p110

Summary

Gene Symbol: p110
Description: phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha
Alias: CLOVE, CWS5, MCAP, MCM, MCMTC, PI3K, p110-alpha, PI3-kinase p110 subunit alpha, PI3K-alpha, phosphatidylinositol 3-kinase, catalytic, 110-KD, alpha, phosphatidylinositol 3-kinase, catalytic, alpha polypeptide, phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit alpha, phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, phosphatidylinositol-4,5-bisphosphate 3-kinase 110 kDa catalytic subunit alpha, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit, alpha isoform, phosphoinositide-3-kinase, catalytic, alpha polypeptide, ptdIns-3-kinase subunit p110-alpha, serine/threonine protein kinase PIK3CA
Species: human

Top Publications

  1. ncbi High frequency of mutations of the PIK3CA gene in human cancers
    Yardena Samuels
    Sidney Kimmel Comprehensive Cancer Center, Howard Hughes Medical Institute, The Johns Hopkins University Medical Institutions, Baltimore, MD 21231, USA
    Science 304:554. 2004
  2. ncbi PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma
    Lao H Saal
    Integrated Program in Cellular, Molecular, and Biophysical Studies, Institute for Cancer Genetics, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
    Cancer Res 65:2554-9. 2005
  3. ncbi Mutation of the PIK3CA gene in ovarian and breast cancer
    Ian G Campbell
    VBCRC Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
    Cancer Res 64:7678-81. 2004
  4. ncbi PIK3CA mutations and copy number gains in human lung cancers
    Hiromasa Yamamoto
    Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center at Dallas, 6000 Harry Hines Boulevard, Dallas, TX 75390 8593, USA
    Cancer Res 68:6913-21. 2008
  5. ncbi Class I PI3K in oncogenic cellular transformation
    L Zhao
    Division of Oncovirology, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    Oncogene 27:5486-96. 2008
  6. ncbi PIK3CA mutation and amplification in human lung cancer
    Koji Okudela
    Department of Pathology I, Hamamatsu Universit School of Medicine, Hamamatsu, Japan
    Pathol Int 57:664-71. 2007
  7. ncbi Uncommon mutation, but common amplifications, of the PIK3CA gene in thyroid tumors
    Guojun Wu
    Department of Otolaryngology Head and Neck Surgery, The Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 333, Baltimore, Maryland 21287, USA
    J Clin Endocrinol Metab 90:4688-93. 2005
  8. ncbi PIK3CA mutation is associated with poor prognosis among patients with curatively resected colon cancer
    Shuji Ogino
    Department of Medical Oncology, Dana Farber Cancer Institute, Brigham and Women s Hospital, Harvard Medical School, 44 Binney St, Room JF 215C, Boston, MA 02115 USA
    J Clin Oncol 27:1477-84. 2009
  9. ncbi Phosphatidylinositol-3-kinase as a therapeutic target in melanoma
    Saadia A Aziz
    Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA
    Clin Cancer Res 15:3029-36. 2009
  10. ncbi Mutant PIK3CA promotes cell growth and invasion of human cancer cells
    Yardena Samuels
    The Sidney Kimmel Comprehensive Cancer Center and The Howard Hughes Medical Institute, The Johns Hopkins University Medical Institutions, Baltimore, MD 21231, USA
    Cancer Cell 7:561-73. 2005

Research Grants

  1. ROLE OF PI3 KINASE AND ITS DOWNSTREAM TARGET BCL-XL IN RPE
    YUN LE; Fiscal Year: 2002
  2. MOLECULAR MECHANISMS OF POLYOMA INDUCED TRANSFORMATION
    Thomas M Roberts; Fiscal Year: 2010
  3. Nuclear GTPase PIKE Regulation and Functions
    Keqiang Ye; Fiscal Year: 2010
  4. Targeted Intervention of Breast Oncogenic Pathways
    Said Sebti; Fiscal Year: 2007
  5. The crosstalk between the PI3K/Akt signal and Skp2 in prostate cancer progression
    Hui Kuan Lin; Fiscal Year: 2010
  6. Insulin Signaling and the Heart in Diabetes
    EVAN DALE ABEL; Fiscal Year: 2010
  7. Heregulin signaling via small GTPases in mitogenesis and tumorigenesis
    MARCELO GABRIEL KAZANIETZ; Fiscal Year: 2010
  8. Heregulin signaling via small GTPases in mitogenesis and tumorigenesis
    MARCELO KAZANIETZ; Fiscal Year: 2009
  9. Effects of the PI3K Pathway on p27 Function and Cancer Progression
    JOYCE MARIE SLINGERLAND; Fiscal Year: 2010
  10. ATF4 and Osteoclastogenesis
    Guozhi Xiao; Fiscal Year: 2010

Detail Information

Publications243 found, 100 shown here

  1. ncbi High frequency of mutations of the PIK3CA gene in human cancers
    Yardena Samuels
    Sidney Kimmel Comprehensive Cancer Center, Howard Hughes Medical Institute, The Johns Hopkins University Medical Institutions, Baltimore, MD 21231, USA
    Science 304:554. 2004
  2. ncbi PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma
    Lao H Saal
    Integrated Program in Cellular, Molecular, and Biophysical Studies, Institute for Cancer Genetics, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
    Cancer Res 65:2554-9. 2005
    Deregulation of the phosphatidylinositol 3-kinase (PI3K) pathway either through loss of PTEN or mutation of the catalytic subunit alpha of PI3K (PIK3CA) occurs frequently in human cancer...
  3. ncbi Mutation of the PIK3CA gene in ovarian and breast cancer
    Ian G Campbell
    VBCRC Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
    Cancer Res 64:7678-81. 2004
    ..5% of all ovarian cancers and 45% of the endometrioid and clear cell subtypes. Our study is the first direct evidence that PIK3CA is an oncogene in ovarian cancer and greatly extends recent findings in breast cancer...
  4. ncbi PIK3CA mutations and copy number gains in human lung cancers
    Hiromasa Yamamoto
    Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center at Dallas, 6000 Harry Hines Boulevard, Dallas, TX 75390 8593, USA
    Cancer Res 68:6913-21. 2008
    ..PIK3CA mutations or gains are present in a subset of lung cancers and are of functional importance...
  5. ncbi Class I PI3K in oncogenic cellular transformation
    L Zhao
    Division of Oncovirology, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    Oncogene 27:5486-96. 2008
    ..The catalytic subunit occurs in four isoforms designated as p110 alpha, p110 beta, p110 gamma and p110 delta...
  6. ncbi PIK3CA mutation and amplification in human lung cancer
    Koji Okudela
    Department of Pathology I, Hamamatsu Universit School of Medicine, Hamamatsu, Japan
    Pathol Int 57:664-71. 2007
    ..The present demonstrates an important role of PIK3CA in human lung carcinogenesis...
  7. ncbi Uncommon mutation, but common amplifications, of the PIK3CA gene in thyroid tumors
    Guojun Wu
    Department of Otolaryngology Head and Neck Surgery, The Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 333, Baltimore, Maryland 21287, USA
    J Clin Endocrinol Metab 90:4688-93. 2005
    As in many other human cancers, overactivation of the phosphotidylinositol 3-kinase (PI3K)/Akt signaling pathway occurs frequently in thyroid cancer, but the mechanism is not completely clear.
  8. ncbi PIK3CA mutation is associated with poor prognosis among patients with curatively resected colon cancer
    Shuji Ogino
    Department of Medical Oncology, Dana Farber Cancer Institute, Brigham and Women s Hospital, Harvard Medical School, 44 Binney St, Room JF 215C, Boston, MA 02115 USA
    J Clin Oncol 27:1477-84. 2009
    ..PIK3CA mutation and subsequent activation of the AKT pathway play an important role in colorectal carcinogenesis. However, little is known about the prognostic role of PIK3CA mutation in colon cancer...
  9. ncbi Phosphatidylinositol-3-kinase as a therapeutic target in melanoma
    Saadia A Aziz
    Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA
    Clin Cancer Res 15:3029-36. 2009
    Phosphatidylinositol-3 kinases (PI3K) are critical for malignant cellular processes including growth, proliferation, and survival, and are targets of drugs in clinical development...
  10. ncbi Mutant PIK3CA promotes cell growth and invasion of human cancer cells
    Yardena Samuels
    The Sidney Kimmel Comprehensive Cancer Center and The Howard Hughes Medical Institute, The Johns Hopkins University Medical Institutions, Baltimore, MD 21231, USA
    Cancer Cell 7:561-73. 2005
    ..PIK3CA mutations resulted in attenuation of apoptosis and facilitated tumor invasion. Treatment with the PI3K inhibitor LY294002 abrogated PIK3CA signaling and preferentially inhibited growth of PIK3CA mutant cells...
  11. ncbi Mutation of the PIK3CA gene in anaplastic thyroid cancer
    Ginesa Garcia-Rostan
    Institute of Molecular Pathology and Immunology of Porto University, Porto, Portugal
    Cancer Res 65:10199-207. 2005
    The phosphatidylinositol 3'-kinase (PI3K) pathway is frequently activated in thyroid carcinomas through the constitutive activation of stimulatory molecules (e.g...
  12. ncbi PIK3CA mutations in breast cancer are associated with poor outcome
    Shao Ying Li
    School of Surgery and Pathology, University of Western Australia, Nedlands, Australia
    Breast Cancer Res Treat 96:91-5. 2006
    The phosphatidylinositol-3-kinase (PI3K)-AKT signaling pathway is considered to play an important role in tumorigenesis. Frequent somatic mutations in the PI3K subunit p110alpha (PIK3CA) occur in a variety of cancer types...
  13. ncbi PIK3CA gene amplification in Japanese non-small cell lung cancer
    Osamu Kawano
    Lung Cancer 58:159-60. 2007
    ..Among 11 patients with PIK3CA amplification, two patients harbored a PIK3CA mutation. There was significant difference in survival between the patients with PIK3CA normal copy number and the patients with PIK3CA amplification...
  14. ncbi The prevalence of PIK3CA mutations in gastric and colon cancer
    Sergia Velho
    Institute of Molecular Pathology and Immunology of the University of Porto IPATIMUP, Portugal
    Eur J Cancer 41:1649-54. 2005
    A wide variety of tumours show PIK3CA mutations leading to increased phosphatidylinositol-3 kinase (PI3K) activity...
  15. ncbi The oncogenic properties of mutant p110alpha and p110beta phosphatidylinositol 3-kinases in human mammary epithelial cells
    Jean J Zhao
    Department of Cancer Biology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:18443-8. 2005
    ..Mutations in the PIK3CB gene encoding p110beta, the only other widely expressed Class IA PI3K, have not been reported...
  16. ncbi Hyaluronic acid and thrombin upregulate MT1-MMP through PI3K and Rac-1 signaling and prime the homing-related responses of cord blood hematopoietic stem/progenitor cells
    Neeta Shirvaikar
    Canadian Blood Services R and D, Edmonton, Canada
    Stem Cells Dev 20:19-30. 2011
    ....
  17. ncbi Association between gain-of-function mutations in PIK3CA and resistance to HER2-targeted agents in HER2-amplified breast cancer cell lines
    Y Kataoka
    Hospital Pharmacy, National Cancer Hospital East, Kashiwa, Japan
    Ann Oncol 21:255-62. 2010
    ....
  18. ncbi Oncogenic PIK3CA mutations occur in epidermal nevi and seborrheic keratoses with a characteristic mutation pattern
    Christian Hafner
    Department of Dermatology, University of Regensburg, 93042 Regensburg, Germany
    Proc Natl Acad Sci U S A 104:13450-4. 2007
    Activating mutations of the p110 alpha subunit of PI3K (PIK3CA) oncogene have been identified in a broad spectrum of malignant tumors. However, their role in benign or preneoplastic conditions is unknown...
  19. ncbi Differential enhancement of breast cancer cell motility and metastasis by helical and kinase domain mutations of class IA phosphoinositide 3-kinase
    Huan Pang
    Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Cancer Res 69:8868-76. 2009
    Class IA (p85/p110) phosphoinositide 3-kinases play a major role in regulating cell growth, survival, and motility...
  20. ncbi Cancer-derived mutations in the regulatory subunit p85alpha of phosphoinositide 3-kinase function through the catalytic subunit p110alpha
    Minghao Sun
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 107:15547-52. 2010
    ..Studies with isoform-specific inhibitors of p110 suggest that expression of p85 mutants in fibroblasts leads exclusively to an activation of p110alpha, and ..
  21. ncbi A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer
    Katrien Berns
    Division of Molecular Carcinogenesis and Center for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Cancer Cell 12:395-402. 2007
    ..In a cohort of 55 breast cancer patients, activation of the PI3K pathway, as judged by the presence of oncogenic PIK3CA mutations or low PTEN expression, was associated with poor ..
  22. ncbi Spectrum of phosphatidylinositol 3-kinase pathway gene alterations in bladder cancer
    Fiona M Platt
    Cancer Research UK Clinical Centre, Leeds Institute of Molecular Medicine, United Kingdom
    Clin Cancer Res 15:6008-17. 2009
    The phosphatidylinositol 3-kinase (PI3K) pathway can be activated by alterations affecting several pathway components...
  23. ncbi Functional analysis of PIK3CA gene mutations in human colorectal cancer
    Tsuneo Ikenoue
    Department of Gastroenterology, Graduate School of Medicine, University of Tokyo Hospital, Bunkyo ku, Japan
    Cancer Res 65:4562-7. 2005
    Mutations in the PIK3CA gene, which encodes the p110alpha catalytic subunit of phosphatidylinositol 3-kinase (PI3K), have been reported in human cancers, including colorectal cancer...
  24. ncbi PIK3CA mutation is predictive of poor survival in patients with colorectal cancer
    Shunsuke Kato
    Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
    Int J Cancer 121:1771-8. 2007
    The PI3K-AKT pathway is activated in a variety of human cancers, resulting in disturbance of cell growth, proliferation and survival...
  25. ncbi PIK3CA gene mutations in pediatric and adult glioblastoma multiforme
    Gary L Gallia
    Department of Neurosurgery, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB II, Room 257, Baltimore, MD 21231, USA
    Mol Cancer Res 4:709-14. 2006
    The phosphatidylinositol 3-kinases (PI3K) are a family of enzymes that relay important cellular growth control signals...
  26. ncbi Frequent mutations and amplifications of the PIK3CA gene in pituitary tumors
    Yong Lin
    Department of Laboratory Medicine, Shanghai Medical College, Fudan University, Shanghai 200040, People s Republic of China
    Endocr Relat Cancer 16:301-10. 2009
    Genetic alterations in the PIK3CA gene of the phosphoinositide 3-kinase (PI3K)/AKT pathway have been found in many human tumors, but they have not been explored in pituitary tumors...
  27. ncbi Genetic variations in the PI3K/PTEN/AKT/mTOR pathway are associated with clinical outcomes in esophageal cancer patients treated with chemoradiotherapy
    Michelle A T Hildebrandt
    Department of Epidemiology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    J Clin Oncol 27:857-71. 2009
    The phosphoinositide-3-kinase (PI3K), phosphatase and tensin homolog (PTEN), v-akt murine thymoma viral oncogene homolog (AKT), and mammalian target of rapamycin (mTOR) signaling pathway has been implicated in resistance to several ..
  28. ncbi Isoform-specific phosphoinositide 3-kinase inhibitors exert distinct effects in solid tumors
    Kyle A Edgar
    Cancer Signaling and Translational Oncology, Genentech, Inc, South San Francisco, California 94080, USA
    Cancer Res 70:1164-72. 2010
    Therapeutic inhibitors are being developed against the phosphoinositide 3-kinase (PI3K) pathway, the deregulation of which drives tumor growth and survival in many cancers. There are eight PI3Ks in mammals divided into three classes...
  29. ncbi PIK3CA mutation in colorectal cancer: relationship with genetic and epigenetic alterations
    Katsuhiko Nosho
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Neoplasia 10:534-41. 2008
    ..In addition, Pyrosequencing is useful in detecting PIK3CA mutation in archival paraffin tumor tissue. PIK3CA mutational data further emphasize heterogeneity of colorectal cancer at the molecular level...
  30. ncbi Small-molecule inhibitors of phosphatidylinositol 3-kinase/Akt signaling inhibit Wnt/beta-catenin pathway cross-talk and suppress medulloblastoma growth
    Ninib Baryawno
    Childhood Cancer Research Unit, Department of Women s and Children s Health, Karolinska Institutet, Stockholm, Sweden
    Cancer Res 70:266-76. 2010
    ..In this study, we show that molecular cross-talk between the beta-catenin and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways is crucial to sustain medulloblastoma pathophysiology...
  31. ncbi Rare PIK3CA hotspot mutations in carcinomas of the biliary tract
    Marc Oliver Riener
    Department of Pathology, Institute of Surgical Pathology, University Hospital Zurich, 8091 Zurich, Switzerland
    Genes Chromosomes Cancer 47:363-7. 2008
    ..Somatic mutations of the PIK3CA gene, which encodes the p110alpha catalytic subunit of phosphatidylinositol 3-kinase (PI3K), are frequent in various cancer types...
  32. ncbi Phosphatidylinositol-3-OH kinase or RAS pathway mutations in human breast cancer cell lines
    Antoinette Hollestelle
    Department of Medical Oncology, Josephine Nefkens Institute Be414, Erasmus MC, P O Box 1738, 3000 DR Rotterdam, The Netherlands
    Mol Cancer Res 5:195-201. 2007
    Constitutive activation of the phosphatidylinositol-3-OH kinase (PI3K) and RAS signaling pathways are important events in tumor formation...
  33. ncbi Mutations of PIK3CA in gastric adenocarcinoma
    Vivian Sze Wing Li
    Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Hong Kong
    BMC Cancer 5:29. 2005
    Activation of the phosphatidylinositol 3-kinase (PI3K) through mutational inactivation of PTEN tumour suppressor gene is common in diverse cancer types, but rarely reported in gastric cancer...
  34. ncbi PIK3CA is implicated as an oncogene in ovarian cancer
    L Shayesteh
    UCSF Cancer Center, University of California, San Francisco 941430 0808, USA
    Nat Genet 21:99-102. 1999
    ..Our observations suggest PIK3CA is an oncogene that has an important role in ovarian cancer...
  35. ncbi Clinicopathologic analysis of breast cancers with PIK3CA mutations in Japanese women
    Naomi Maruyama
    Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2 2 Yamadaoka, Suita Shi, Osaka 565 0871, Japan
    Clin Cancer Res 13:408-14. 2007
    ..In this study, the frequency of PIK3CA mutations and their relationship with clinicopathologic and biological variables were investigated in Japanese breast cancers...
  36. ncbi PIK3CA cooperates with other phosphatidylinositol 3'-kinase pathway mutations to effect oncogenic transformation
    Katsutoshi Oda
    Cancer Research Institute, Howard Hughes Medical Institute, University of California at San Francisco, San Francisco, California, USA
    Cancer Res 68:8127-36. 2008
    ..Our data therefore suggest that in tumors with co-occurring mutations in multiple components of the PI3K pathway, selective inhibition of the alpha isoform of p110 is an attractive therapeutic strategy, especially for late-stage tumors.
  37. ncbi Markers for EGFR pathway activation as predictor of outcome in metastatic colorectal cancer patients treated with or without cetuximab
    Jolien Tol
    Department of Medical Oncology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
    Eur J Cancer 46:1997-2009. 2010
    ..Here we assess the predictive value of other potential relevant markers involved in the epidermal growth factor receptor (EGFR) signalling pathways for response to cetuximab-based treatment...
  38. ncbi The PIK3CA gene is mutated with high frequency in human breast cancers
    Kurtis E Bachman
    The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Department of Oncology, Baltimore, Maryland 21231, USA
    Cancer Biol Ther 3:772-5. 2004
    ..It has recently been reported that somatic mutations within the PI3K subunit p110alpha (PIK3CA) are present in human colorectal and other cancers...
  39. ncbi PIK3CA alterations in Middle Eastern ovarian cancers
    Jehad Abubaker
    Department of Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
    Mol Cancer 8:51. 2009
    b>PI3K/AKTsignaling pathway plays an important role in cell growth, proliferation, and tumorgenesis of various malignancies. This signaling pathway has been shown to be frequently altered in several human cancers including ovarian cancers...
  40. ncbi Cancer-specific mutations in PIK3CA are oncogenic in vivo
    Andreas G Bader
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 103:1475-9. 2006
    ..The in vivo oncogenicity of PIK3CA mutants in an avian species strongly suggests a critical role for these mutated proteins in human malignancies...
  41. ncbi Functional differences between two classes of oncogenic mutation in the PIK3CA gene
    Claire Chaussade
    Department of Molecular Medicine, University of Auckland, New Zealand
    Biochem Biophys Res Commun 381:577-81. 2009
    ..Together these results suggest helical domain mutants are in a state mimicking activation by growth factors whereas kinase domain mutants mimic the state activated by H-Ras...
  42. ncbi Aurora-A down-regulates IkappaBalpha via Akt activation and interacts with insulin-like growth factor-1 induced phosphatidylinositol 3-kinase pathway for cancer cell survival
    Jin E Yao
    State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat Sen University, 651 Dongfeng Road East, Guangzhou, PR China
    Mol Cancer 8:95. 2009
    ..As a bona fide oncoprotein, Aurora-A aberrant overexpression leads to oncogenic transformation. Yet, the mechanisms by which Aurora-A enhances cancer cell survival remain to be elucidated...
  43. ncbi Frequent activating mutations of PIK3CA in ovarian clear cell carcinoma
    Kuan Ting Kuo
    Departments of Pathology, Howard Hughes Medical Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
    Am J Pathol 174:1597-601. 2009
    ..We therefore suggest that the use of PIK3CA-targeting drugs may offer a more effective therapeutic approach compared with current chemotherapeutic agents for patients with advanced-stage and recurrent CCC...
  44. ncbi Identification and characterization of NVP-BKM120, an orally available pan-class I PI3-kinase inhibitor
    Sauveur Michel Maira
    Novartis Institute for Biomedical Research, Oncology Disease Area, Novartis Pharma AG, Klybeckstrasse 141, CH 4002 Basel, Switzerland
    Mol Cancer Ther 11:317-28. 2012
    Following the discovery of NVP-BEZ235, our first dual pan-PI3K/mTOR clinical compound, we sought to identify additional phosphoinositide 3-kinase (PI3K) inhibitors from different chemical classes with a different selectivity profile...
  45. ncbi PI3K/AKT/mTOR inhibitors in patients with breast and gynecologic malignancies harboring PIK3CA mutations
    Filip Janku
    The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    J Clin Oncol 30:777-82. 2012
    Mutations of the PIK3CA gene may predict response to phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) inhibitors...
  46. ncbi A unique spectrum of somatic PIK3CA (p110alpha) mutations within primary endometrial carcinomas
    Meghan L Rudd
    Cancer Genetics Branch, National Human Genome Research Institute, National Cancer Institute, Bethesda, Maryland, USA
    Clin Cancer Res 17:1331-40. 2011
    ..The goal of this study was to comprehensively define the incidence of mutations in all exons of PIK3CA in both endometrioid endometrial cancer (EEC) and nonendometrioid endometrial cancer (NEEC)...
  47. ncbi Mutual exclusiveness between PIK3CA and KRAS mutations in endometrial carcinoma
    S Kang
    Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Korea
    Int J Gynecol Cancer 18:1339-43. 2008
    ..PIK3CA was frequently mutated in endometrial cancers. KRAS and PIK3CA mutations are inversely correlated, suggesting that genetic alterations of KRAS and PIK3CA may play equivalent roles in endometrial carcinogenesis...
  48. ncbi KRAS, BRAF and PIK3CA mutations in human colorectal cancer: relationship with metastatic colorectal cancer
    Hong Tao Li
    State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, 127 ChangLe West Road, Xi an, Shaanxi Province 710032, PR China
    Oncol Rep 25:1691-7. 2011
    ..Notably, our data indicated that colorectal cancers with KRAS and PIK3CA bi-mutations are more likely to develop into liver metastasis...
  49. ncbi PIK3CA mutations are mutually exclusive with PTEN loss in diffuse large B-cell lymphoma
    J Abubaker
    Leukemia 21:2368-70. 2007
  50. ncbi Gene expression profiling reveals new aspects of PIK3CA mutation in ERalpha-positive breast cancer: major implication of the Wnt signaling pathway
    Magdalena Cizkova
    Laboratoire d oncogénétique, Institut National de la Santé et de la Recherche, U745, Institut Curie Hôpital René Huguenin, St Cloud, France
    PLoS ONE 5:e15647. 2010
    The PI3K/AKT pathway plays a pivotal role in breast cancer development and maintenance...
  51. ncbi Up-regulation of PIK3CA promotes metastasis in gastric carcinoma
    Ji Fang Liu
    Institute of Cancer Research, Affiliated Tumor Hospital of Guangzhou Medical College, Guangzhou 510095, Guangdong Province, China
    World J Gastroenterol 16:4986-91. 2010
    To explore expressions of PIK3CA in the progression of gastric cancer from primary to metastasis and its effects on activation of phosphatidylinositol 3-kinase (PI3K)/Akt pathway.
  52. ncbi PIK3CA mutation is an oncogenic aberration at advanced stages of oral squamous cell carcinoma
    Ken ichi Kozaki
    Department of Genome Medicine, Graduate School, Tokyo Medical and Dental University, 1 5 45 Yushima Bunkyo ku, Tokyo 113 8510, Japan
    Cancer Sci 97:1351-8. 2006
    Phosphatidylinositol 3-kinases (PI3K) are a group of heterodimeric lipid kinases that regulate many cellular processes...
  53. ncbi Rare mutations in the PIK3CA gene contribute to aggressive endometrial cancer
    Darina Konstantinova
    1 Department of Chemistry and Biochemistry, Medical University Sofia, Sofia, Bulgaria
    DNA Cell Biol 29:65-70. 2010
    ..3%; p = 0.02). In all other comparisons exons 9 and 20 mutation distribution did not differ. These results suggest the need for further exploration of the significance of PIK3CA mutations in respect to aggressive EC...
  54. ncbi Clinical significance of genetic variations in the PI3K/PTEN/AKT/mTOR pathway in Korean patients with colorectal cancer
    Jong Gwang Kim
    Department of Oncology Hematology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Korea
    Oncology 79:278-82. 2010
    Signaling through the PI3K/PTEN/AKT/mTOR pathway is responsible for balancing cell survival and apoptosis...
  55. ncbi HIV-1 Tat induces tyrosine phosphorylation of p125FAK and its association with phosphoinositide 3-kinase in PC12 cells
    D Milani
    Department of Morphology and Embriology, University of Ferrara, Italy
    AIDS 12:1275-84. 1998
    ..To evaluate the signal transduction potential of HIV-1 Tat in a neuronal cell model...
  56. ncbi Stanniocalcin 1 induction by thyroid hormone depends on thyroid hormone receptor β and phosphatidylinositol 3-kinase activation
    L C Moeller
    Department of Endocrinology and Division of Laboratory Research, University of Duisburg Essen, Essen, Germany
    Exp Clin Endocrinol Diabetes 119:81-5. 2011
    ..A recently described extranuclear mechanism of TH action consists of the association of TH-liganded TRβ with phosphatidylinositol 3-kinase (PI3K) in the cytosol and subsequent activation of the PI3K pathway.
  57. ncbi PIK3CA mutation and histological type in breast carcinoma: high frequency of mutations in lobular carcinoma
    Fiamma Buttitta
    Clinical Research Center, Center of Excellence on Aging, University Foundation, Chieti, Italy
    J Pathol 208:350-5. 2006
    ....
  58. ncbi A frequent kinase domain mutation that changes the interaction between PI3Kalpha and the membrane
    Diana Mandelker
    The Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA
    Proc Natl Acad Sci U S A 106:16996-7001. 2009
    ..These structural and biochemical data suggest a previously undescribed mechanism for mutational activation of a kinase that involves perturbation of its interaction with the cellular membrane...
  59. ncbi HIV-1-Tat protein activates phosphatidylinositol 3-kinase/ AKT-dependent survival pathways in Kaposi's sarcoma cells
    Maria Chiara Deregibus
    Cattedra di Nefrologia, Dipartimento di Medicina Interna Università di Torino, Centro Ricerca Medicina Sperimentale CeRMS, Italy
    J Biol Chem 277:25195-202. 2002
    ....
  60. ncbi Oncogenic PI3K deregulates transcription and translation
    Andreas G Bader
    Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Rev Cancer 5:921-9. 2005
    There have long been indications of a role for PI3K (phosphatidylinositol 3-kinase) in cancer pathogenesis...
  61. ncbi Frequent mutation of the PIK3CA gene in ovarian and breast cancers
    Douglas A Levine
    Gynecology and Breast Research Laboratory, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Clin Cancer Res 11:2875-8. 2005
    Activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway, resulting in increased cell proliferation, survival, and motility, is believed to play an oncogenic role in many cancer types...
  62. ncbi PI3KCA/PTEN deregulation contributes to impaired responses to cetuximab in metastatic colorectal cancer patients
    F Perrone
    Experimental Molecular Pathology, Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
    Ann Oncol 20:84-90. 2009
    ..affect response to anti-epidermal growth factor receptor (EGFR) mAbs in metastatic colorectal cancer (mCRC) patients, while the biological impact of the EGFR pathway represented by PI3K/PTEN/AKT on anti-EGFR treatment is still not clear.
  63. ncbi Prognostic and predictive value of common mutations for treatment response and survival in patients with metastatic colorectal cancer
    J Souglakos
    Department of Medical Oncology, University Hospital of Heraklion, Voutes and Stavrakia, Heraklion, Crete, Greece
    Br J Cancer 101:465-72. 2009
    ..We address the prognostic and predictive value of KRAS, PIK3CA and BRAF mutations for clinical outcomes in response to active agents in the treatment of metastatic colorectal cancer (mCRC)...
  64. ncbi Somatic mutations of ERBB2 kinase domain in gastric, colorectal, and breast carcinomas
    Jong Woo Lee
    Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea
    Clin Cancer Res 12:57-61. 2006
    ..However, because previous reports focused the mutational search of ERBB2 primarily on lung cancers, the data on ERBB2 mutations in other types of human cancers have been largely unknown...
  65. ncbi HIV-1 Nef downregulates MHC-I by a PACS-1- and PI3K-regulated ARF6 endocytic pathway
    Anastassia D Blagoveshchenskaya
    Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
    Cell 111:853-66. 2002
    ..Here, we show that Nef and PACS-1 combine to usurp the ARF6 endocytic pathway by a PI3K-dependent process and downregulate cell surface MHC-I to the TGN...
  66. ncbi PIK3CA mutations are not a major determinant of resistance to the epidermal growth factor receptor inhibitor cetuximab in metastatic colorectal cancer
    Hans Prenen
    Department of Digestive Oncology, University Hospital Gasthuisberg, Leuven, Belgium
    Clin Cancer Res 15:3184-8. 2009
    ..Other mechanisms of resistance to EGFR inhibitors could involve activating mutations of the other main EGFR effector pathway, i.e., the PI3K/PTEN/AKT pathway.
  67. ncbi Phosphatidylinositol 3-kinase regulates human immunodeficiency virus type 1 replication following viral entry in primary CD4+ T lymphocytes and macrophages
    Fleur Francois
    Division of Infectious Diseases, Mt Sinai School of Medicine, 1 Gustave L Levy Place, New York, NY 10029, USA
    J Virol 77:2539-49. 2003
    ..This type of host-virus interaction has implications for anti-HIV therapeutics that target cellular signaling machinery...
  68. ncbi Mutational analysis of EGFR and related signaling pathway genes in lung adenocarcinomas identifies a novel somatic kinase domain mutation in FGFR4
    Jenifer L Marks
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America
    PLoS ONE 2:e426. 2007
    ..We performed mutational profiling of a large cohort of lung adenocarcinomas to uncover other potential somatic mutations in genes of this signaling pathway that could contribute to lung tumorigenesis...
  69. ncbi Genetic alterations of phosphoinositide 3-kinase subunit genes in human glioblastomas
    Masahiro Mizoguchi
    Molecular Neuro oncology Laboratory, Department of Pathology and Neurosurgical Service, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Brain Pathol 14:372-7. 2004
    Genetic alterations of PI3K (phosphoinositide 3-kinase) subunits have been documented in a number of tumor types, with increased PI3K activity linked to gene amplification and mutation of catalytic subunits, as well as mutations of ..
  70. ncbi PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal antibodies
    Andrea Sartore-Bianchi
    The Falck Division of Medical Oncology, Ospedale Niguarda Ca Granda, Milan, Italy
    Cancer Res 69:1851-7. 2009
    ..When the molecular status of the PIK3CA/PTEN and KRAS pathways are concomitantly ascertained, up to 70% of mCRC patients unlikely to respond to EGFR moAbs can be identified...
  71. ncbi The anti-apoptotic effect of Notch-1 requires p56lck-dependent, Akt/PKB-mediated signaling in T cells
    Hadassah Sade
    National Centre for Biological Sciences, University of Agricultural Sciences Gandhi Krishi Vignan Kendra Campus, New Bellary Road, Bangalore 560065, Karnataka, India
    J Biol Chem 279:2937-44. 2004
    ..inhibitors and dominant-negative approaches, we describe a functional role for phosphatidylinositol 3-kinase (PI3K)-dependent activation of the serine-threonine kinase Akt/PKB in the regulation of AcN1-mediated anti-apoptotic ..
  72. ncbi Molecular analysis of the PI3K-AKT pathway in uterine cervical neoplasia: frequent PIK3CA amplification and AKT phosphorylation
    Bjørn I Bertelsen
    Department of Pathology, The Gade Institute, University of Bergen and Haukeland University Hospital, Bergen, Norway
    Int J Cancer 118:1877-83. 2006
    ..The putative oncogene PIK3CA located in this region encodes a phosphatidylinositol 3-kinase (PI3K)...
  73. ncbi HIV-1 Tat promotes monocyte chemoattractant protein-1 secretion followed by transmigration of monocytes
    I W Park
    Division of Experimental Medicine and Hematology Oncology, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, MA 02115, USA
    Blood 97:352-8. 2001
    ..These data indicate that the HIV-1 Tat protein may act as a protocytokine by causing the release of MCP-1 from the endothelial monolayer, and thereby facilitating monocyte transmigration into tissues via a PKC signaling pathway...
  74. ncbi Concomitant activation of AKT with extracellular-regulated kinase 1/2 occurs independently of PTEN or PIK3CA mutations in endometrial cancer and may be associated with favorable prognosiss
    Noriko Mori
    Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kanazawa University, 13 1 Takaramachi, Kanazawa, Ishikawa 920 8641, Japan
    Cancer Sci 98:1881-8. 2007
    Deregulated signaling via the phosphatidylinositol 3-kinase (PI3K) pathway is common in many types of cancer, but its clinicopathological significance in endometrial cancer remains unclear...
  75. ncbi Purification and characterization of phosphoinositide 3-kinase from rat liver
    C L Carpenter
    Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111
    J Biol Chem 265:19704-11. 1990
    ..Substitution of Mn2+ for Mg2+ results in only approximately 10% of the Mg2(+)-dependent activity. Physiological calcium concentrations have no effect on the enzyme activity. Phosphoinositide 3-kinase has a broad pH optimum around 7...
  76. ncbi Nutrients suppress phosphatidylinositol 3-kinase/Akt signaling via raptor-dependent mTOR-mediated insulin receptor substrate 1 phosphorylation
    Alexandros Tzatsos
    Boston University School of Medicine, Massachusetts 02118, USA
    Mol Cell Biol 26:63-76. 2006
    ..Thus, diabetes-related hyperglycemia hyperactivates the mTOR pathway and may lead to insulin resistance due to suppression of IRS-1-dependent PI3-kinase/Akt signaling...
  77. ncbi Extracellular HIV-1 Tat protein activates phosphatidylinositol 3- and Akt/PKB kinases in CD4+ T lymphoblastoid Jurkat cells
    P Borgatti
    Institute of Human Anatomy, University of Ferrara, Italy
    Eur J Immunol 27:2805-11. 1997
    ..Taken together, these data suggest that the anti-apoptotic activity of low concentrations of Tat protein on Jurkat cells is mediated by a PI 3-kinase/Akt pathway...
  78. ncbi HIV-1 gp120-mediated apoptosis of T cells is regulated by the membrane tyrosine phosphatase CD45
    Appakkudal R Anand
    Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 281:12289-99. 2006
    ..These results suggest a novel CD45-mediated mechanism for the HIV envelope-induced apoptosis of T cells...
  79. ncbi PIK3CA gene mutations in endometrial carcinoma: correlation with PTEN and K-RAS alterations
    Ana Velasco
    Department of Pathology and Molecular Genetics, Hospital Universitari Arnau de Vilanova, University of Lleida, Lleida, Spain
    Hum Pathol 37:1465-72. 2006
    Alterations in the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway are common in endometrial carcinoma...
  80. ncbi PIK3CA mutation status in Japanese lung cancer patients
    Osamu Kawano
    Department of Surgery II, Nagoya City University Medical School, Nagoya, Japan
    Lung Cancer 54:209-15. 2006
    ..PIK3CA gene mutations were rare in lung cancer; rarer in adenocarcinoma. Further functional analyses of the PIK3CA mutations are warranted to study if they could be the target of therapy for the lung cancer...
  81. ncbi p53 regulates cell survival by inhibiting PIK3CA in squamous cell carcinomas
    Bhuvanesh Singh
    Laboratory of Epithelial Cancer Biology, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Genes Dev 16:984-93. 2002
    Interactions between the p53 and PI3K/AKT pathways play a significant role in the determination of cell death/survival...
  82. ncbi Somatic mutation and gain of copy number of PIK3CA in human breast cancer
    Guojun Wu
    Department of Otolaryngology Head and Neck Surgery, Head and Neck Cancer Research Division, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Breast Cancer Res 7:R609-16. 2005
    ..Even though PIK3CA amplification and somatic mutation have been reported previously in various kinds of human cancers, the genetic change in PIK3CA in human breast cancer has not been clearly identified...
  83. ncbi ADP-ribosylation factor 1 controls the activation of the phosphatidylinositol 3-kinase pathway to regulate epidermal growth factor-dependent growth and migration of breast cancer cells
    Pierre Luc Boulay
    Department of Pharmacology, Faculty of Medicine, University of Montreal, Montreal, Quebec H3C 3J7, Canada
    J Biol Chem 283:36425-34. 2008
    ..These results uncover a novel molecular mechanism by which ARF1 regulates breast cancer cell growth and invasion during cancer progression...
  84. ncbi Different prognostic roles of mutations in the helical and kinase domains of the PIK3CA gene in breast carcinomas
    Mattia Barbareschi
    Unit of Surgical Pathology, Laboratory of Molecular Pathology S Chiara Hospital, Trento, Italy, and Clinical Research Center, Center of Excellence on Aging, University Foundation, Chieti, Italy
    Clin Cancer Res 13:6064-9. 2007
    ..We decided to investigate the association of PIK3CA mutations with pathologic features and clinical outcome in a large series of patients with breast cancer...
  85. ncbi PIK3CA mutations in advanced ovarian carcinomas
    Yun Wang
    Department of Gynecologic Oncology, The Norwegian Radium Hospital, N 0310, Oslo, Norway
    Hum Mutat 25:322. 2005
    ..family, which play an important role in proliferation, adherence, transformation and cell survival through the PI3K/AKT signaling pathway...
  86. ncbi PIK3CA cancer mutations display gender and tissue specificity patterns
    Silvia Benvenuti
    Laboratory of Molecular Genetics, The Oncogenomics Center, Institute for Cancer Research and Treatment IRCC, University of Torino Medical School, Candiolo, Italy
    Hum Mutat 29:284-8. 2008
    ..We have examined whether PI3K oncogenic mutations (exons 9 and 20) might exhibit gender and/or tissue specificity...
  87. ncbi Mutations of PIK3CA in anaplastic oligodendrogliomas, high-grade astrocytomas, and medulloblastomas
    Daniel K Broderick
    Brain Tumor Center, Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
    Cancer Res 64:5048-50. 2004
    ..These observations implicate PIK3CA as an oncogene in a wider spectrum of adult and pediatric brain tumors and suggest that PIK3CA may be a useful diagnostic marker or a therapeutic target in these cancers...
  88. ncbi Phosphatidylinositol 3-kinase-dependent membrane recruitment of Rac-1 and p47phox is critical for alpha-platelet-derived growth factor receptor-induced production of reactive oxygen species
    Anselm T Bäumer
    Klinik III fur Innere Medizin, Universitat zu Koln, 50937 Koln, Germany
    J Biol Chem 283:7864-76. 2008
    ..that lack specific binding sites for alphaPDGFR-associated signaling molecules (Src, phosphatidylinositol 3-kinase (PI3K), phospholipase Cgamma, and SHP-2)...
  89. ncbi Clinicopathological analysis of colorectal cancers with PIK3CA mutations in Middle Eastern population
    J Abubaker
    Department of Human Cancer Genomic Research, King Fahad National Center for Children s Cancer and Research, Riyadh, Saudi Arabia
    Oncogene 27:3539-45. 2008
    Activation of the phosphatidylinositol 3'-kinase (PI3K)/AKT pathway results in an increase in cell proliferation and survival...
  90. ncbi Transcriptional regulation of PIK3CA oncogene by NF-kappaB in ovarian cancer microenvironment
    Nuo Yang
    Center for Research on Early Detection and Cure of Ovarian Cancer, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America
    PLoS ONE 3:e1758. 2008
    ..These results offer a new mechanism through which the tumor microenvironment directly activates oncogenic pathways in tumor cells...
  91. ncbi Angiogenesis selectively requires the p110alpha isoform of PI3K to control endothelial cell migration
    Mariona Graupera
    Centre for Cell Signalling, Institute of Cancer, Queen Mary, University of London, Charterhouse Square, London EC1M 6BQ, UK
    Nature 453:662-6. 2008
    ..Class IA PI3K isoforms couple to tyrosine kinases and consist of a p110 catalytic subunit (p110alpha, p110beta or p110delta), constitutively bound to one of five distinct p85 regulatory ..
  92. ncbi The p85 regulatory subunit of phosphoinositide 3-kinase down-regulates IRS-1 signaling via the formation of a sequestration complex
    Ji Luo
    Department of Systems Biology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA
    J Cell Biol 170:455-64. 2005
    ..Surprisingly, monomeric p85 is preferentially localized to these foci compared with the p85-p110 dimer, and these foci are not sites of phosphatidylinositol-3,4,5-trisphosphate production...
  93. ncbi HIV-1 gp120-induced TNF-{alpha} production by primary human macrophages is mediated by phosphatidylinositol-3 (PI-3) kinase and mitogen-activated protein (MAP) kinase pathways
    ChuHee Lee
    Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    J Leukoc Biol 78:1016-23. 2005
    ..These gp120-triggered signaling pathways may be responsible for inappropriate production of proinflammatory cytokines by macrophages, which are believed to play a role in immunopathogenesis and in neurological sequelae of AIDS...
  94. ncbi Rare mutations of the PIK3CA gene in malignancies of the hematopoietic system as well as endometrium, ovary, prostate and osteosarcomas, and discovery of a PIK3CA pseudogene
    Claudia I Muller
    Division of Hematology Oncology, Cedars Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA 90048, USA
    Leuk Res 31:27-32. 2007
    ..Additionally, a previously unidentified PIK3CA pseudogene spanning exons 9-13 on chromosome 22 was discovered...
  95. ncbi Effect of tumor necrosis factor-alpha on insulin signal transduction in rat adipocytes: relation to PKCbeta and zeta translocation
    A Miura
    The Third Department of Internal Medicine, Gifu University School of Medicine, Gifu 500-8705, Japan
    Biochim Biophys Acta 1449:227-38. 1999
    ..by activation of second messengers such as insulin receptor substrate 1 (IRS-1), phosphatidylinositol 3-kinase (PI3K), and diacylglycerol (DG)-protein kinase C (PKC)...
  96. ncbi PI 3-kinase gamma and protein kinase C-zeta mediate RAS-independent activation of MAP kinase by a Gi protein-coupled receptor
    H Takeda
    Second Department of Internal Medicine, Kobe University School of Medicine, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
    EMBO J 18:386-95. 1999
    ..The RAS-independent activation of MAP kinase by LPA was blocked by inhibitors of phosphatidylinositol 3-kinase (PI3K) or by overexpression of a dominant-negative mutant of the gamma isoform of PI3K...
  97. ncbi Phosphatidylinositide 3-kinase gamma regulates key pathologic responses to cholecystokinin in pancreatic acinar cells
    Ilya Gukovsky
    Department of Medicine, VA Greater Los Angeles Healthcare Sysytem and University of California, Los Angeles, 90073, USA
    Gastroenterology 126:554-66. 2004
    ..We here report that these responses are regulated by phosphatidylinositide 3-kinase (PI3K) gamma.
  98. ncbi Regulation of nuclear factor kappa B transactivation. Implication of phosphatidylinositol 3-kinase and protein kinase C zeta in c-Rel activation by tumor necrosis factor alpha
    A G Martin
    Centro de Biologia Molecular "Severo Ochoa, , Cantoblanco, Madrid 28049, Spain
    J Biol Chem 276:15840-9. 2001
    ..Phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC) zeta were identified as downstream signaling molecules of TNFalpha-activation of c-Rel ..
  99. ncbi Requirement of protein kinase C zeta for stimulation of protein synthesis by insulin
    R Mendez
    Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, Shreveport 71130, USA
    Mol Cell Biol 17:5184-92. 1997
    ..These phosphorylated substrates directly bind and activate enzymes such as phosphatidylinositol 3'-kinase (PI3K) and the guanine nucleotide exchange factor for p21Ras (GRB-2/SOS), which are in turn required for insulin-..
  100. ncbi Protein kinase C-zeta and phosphoinositide-dependent protein kinase-1 are required for insulin-induced activation of ERK in rat adipocytes
    M P Sajan
    J. A. Haley Veterans Hospital Research Service, Department of Internal Medicine, University of South Florida College of Medicine, Tampa, Florida 33612, USA
    J Biol Chem 274:30495-500. 1999
    ..insulin-induced activation of ERK was blocked (a) by chemical inhibitors of both phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC)-zeta, and, moreover, (b) by transient expression of both dominant-negative Deltap85 ..
  101. ncbi PI3K and PKC contribute to membrane depolarization mediated by alpha2-adrenoceptors in the canine isolated mesenteric vein
    Ilia A Yamboliev
    Department of Pharmacology and Center of Biomedical Research Excellence, University of Nevada School of Medicine, Reno, Nevada 89557, USA
    BMC Physiol 5:9. 2005
    ..In the present study we hypothesized that phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC) are involved in the electrical field stimulation (EFS)-induced slow membrane ..

Research Grants68

  1. ROLE OF PI3 KINASE AND ITS DOWNSTREAM TARGET BCL-XL IN RPE
    YUN LE; Fiscal Year: 2002
    ..One messenger, PI-3,4,5-P3, generated by the PI-3 kinase (PI3K), plays an important role in cell protection, cell proliferation, glucose homeostasis, membrane trafficking and ..
  2. MOLECULAR MECHANISMS OF POLYOMA INDUCED TRANSFORMATION
    Thomas M Roberts; Fiscal Year: 2010
    ..our studies of MT and PI3K, and have recently used conditional knockouts of the key catalytic subunits of PI3K, p110? and p110?, to discover a previously unknown subtlety in the roles of these enzymes in signaling and cancer...
  3. Nuclear GTPase PIKE Regulation and Functions
    Keqiang Ye; Fiscal Year: 2010
    PIKE (PI 3-kinase Enhancer) is a brain specific GTPase that enhances PI 3-kinase (PI3K) activity. PIKE binds and stimulates PI3K activity in a GTP-dependent manner...
  4. Targeted Intervention of Breast Oncogenic Pathways
    Said Sebti; Fiscal Year: 2007
    ..goal of this project is to understand the role of the oncogenic and tumor survival pathways, Mek/Erk, JAK/STAT3 and PI3K/Akt in breast oncogenesis and to develop new strategies for more effective breast cancer treatment...
  5. The crosstalk between the PI3K/Akt signal and Skp2 in prostate cancer progression
    Hui Kuan Lin; Fiscal Year: 2010
    ..cancers and associated with cancer metastasis, it is important to identify the key effector downstream of the PTEN/PI3K/Akt pathway that drives cancer progression and metastasis...
  6. Insulin Signaling and the Heart in Diabetes
    EVAN DALE ABEL; Fiscal Year: 2010
    ..Moreover, we identified a central role for PI3K signaling in coordinating the mitochondrial adaptation to physiological cardiac hypertrophy...
  7. Heregulin signaling via small GTPases in mitogenesis and tumorigenesis
    MARCELO GABRIEL KAZANIETZ; Fiscal Year: 2010
    ..HRG-induced Rac activation was PI3K-dependent...
  8. Heregulin signaling via small GTPases in mitogenesis and tumorigenesis
    MARCELO KAZANIETZ; Fiscal Year: 2009
    ..HRG-induced Rac activation was PI3K-dependent...
  9. Effects of the PI3K Pathway on p27 Function and Cancer Progression
    JOYCE MARIE SLINGERLAND; Fiscal Year: 2010
    ..We showed that p27 is phosphorylated by AGC family kinases downstream of PI3K at T157, T198, or both, which impairs nuclear p27 import, stabilizes p27 in the cytoplasm and stimulates cell ..
  10. ATF4 and Osteoclastogenesis
    Guozhi Xiao; Fiscal Year: 2010
    ..regulating osteoclastogenesis by two distinct mechanisms: 1) ATF4 modulates M-CSF induction of RANK expression via PI3K/AKT-dependent phosphorylation and protein stabilization and/or activation;2) ATF4 mediates RANKL induction of ..
  11. Phosphodiesterase-3B signaling in the Hypothalamus and Obesity
    Abhiram Sahu; Fiscal Year: 2010
    ..Our study suggests that a PI3K-PDE3B-cAMP pathway interacting with the JAK2-STAT3 pathway constitutes a critical component of leptin signaling in ..
  12. Molecular Events in the PI3K/Akt Pathway in Thyroid Cancer
    MICHAEL MINGZHAO XING; Fiscal Year: 2010
    ..The PI3K/Akt pathway has recently emerged as a major source of molecular derangements in thyroid cancer...
  13. Role of Integrin-Linked Kinase in Heart Failure and Ischemic Injury
    Anthony Rosenzweig; Fiscal Year: 2010
    ..activation of Akt has deleterious effects associated with feedback inhibition of upstream IRS-1/PI 3-kinase (PI3K) signaling...
  14. Role of Integrin-Linked Kinase in Heart Failure and Ischemic Injury
    Anthony Rosenzweig; Fiscal Year: 2007
    ..activation of Akt has deleterious effects associated with feedback inhibition of upstream IRS-1/PI 3-kinase (PI3K) signaling...
  15. Intervention of Pancreatic Oncogenic Pathways with Dietary Tocotrienol
    Mokenge P Malafa; Fiscal Year: 2010
    ..inhibits several effectors of activated Ras in pancreatic cancer cells such as down regulation of the Mek/Erk and PI3K/Akt mitogenic and tumor survival signaling pathways and up regulation of p27...
  16. Intervention of Pancreatic Oncogenic Pathways with Dietary Tocotrienol
    Mokenge Malafa; Fiscal Year: 2009
    ..inhibits several effectors of activated Ras in pancreatic cancer cells such as down regulation of the Mek/Erk and PI3K/Akt mitogenic and tumor survival signaling pathways and up regulation of p27...
  17. Molecular regulation of CeA glutamate and binge drinking
    Karen Kathleen Szumlinski; Fiscal Year: 2010
    ..data from my laboratory demonstrates that alcohol-induced increases in mGluR5/Homer2 pathway activity (via PI3K and PKC5) within the nucleus accumbens (NAC) shell as important for the propensity to consume alcohol in murine ..
  18. Selective Insulin Resistance- Diabetic Cardiovascular Diseases
    George L King; Fiscal Year: 2010
    ..concept that "selective" inhibition of insulin's anti-atherogenic actions mediated by the activation of IRS/PI3K/Akt pathways could be a major cause of cardiovascular complications in diabetes...
  19. Mechanisms of Diabetic Hyperphagia and Insulin Resistance
    Michael W Schwartz; Fiscal Year: 2010
    ..At the cellular level, signaling via the insulin receptor substrate-phosphotidylinositol-3 kinase (IRS-PI3K) pathway plays a critical role in insulin action in peripheral tissues and while this pathway is also critical for ..
  20. Regulation of plasma cell differentiation by PI3-kinase
    ROBERT RICKERT; Fiscal Year: 2007
    ..The proposed work addresses the role of phosphatidyl inositol-3 kinase (PI3K) in directing the activated B cell fate decision toward plasma cell generation or the germinal center...
  21. The Role of PtdIns-5-P in Cell Function and Signaling
    LUCIA RAMEH PLANT; Fiscal Year: 2009
    ..in PI-5-P levels is accompanied by dramatic changes in the actin cytoskeleton and in phosphoinositide 3-kinase (PI3k) signaling...
  22. The Role of PtdIns-5-P in Cell Function and Signaling
    LUCIA RAMEH PLANT; Fiscal Year: 2010
    ..in PI-5-P levels is accompanied by dramatic changes in the actin cytoskeleton and in phosphoinositide 3-kinase (PI3k) signaling...
  23. The Role of PtdIns-5-P in Cell Function and Signaling
    LUCIA RAMEH PLANT; Fiscal Year: 2009
    ..in PI-5-P levels is accompanied by dramatic changes in the actin cytoskeleton and in phosphoinositide 3-kinase (PI3k) signaling...
  24. Activating PTPN11 and c-kit Mutations in Myeloproliferative Disorder
    Rebecca Chan; Fiscal Year: 2007
    ..GM-CSF hypersensitivity induced by activating PTPN11 mutations by the lipid kinase phosphoinsositol-3-kinase (PI3K) inhibitor, LY294002; therefore, we hypothesize hyperactivation of PI3K activity also contributes to the ..
  25. Molecular mechanisms of C/EBP alpha mediated growth arrest
    Nikolai A Timchenko; Fiscal Year: 2010
    ..proteins and these interactions are controlled by certain signal transduction pathways such as cyclin D3-cdk4/6 and PI3K-Akt-PP2A...
  26. Molecular mechanisms of C/EBP alpha mediated growth arrest
    Nikolai A Timchenko; Fiscal Year: 2011
    ..proteins and these interactions are controlled by certain signal transduction pathways such as cyclin D3-cdk4/6 and PI3K-Akt-PP2A...
  27. ELEVATED CALCIUM AND MYOCARDIAL ISCHEMIC INJURY
    Charles Steenbergen; Fiscal Year: 2006
    ..aim of this proposal is to investigate the protective effect of activation of phosphatidylinositol-3-kinase (PI3K) on myocardial ischemia/reperfusion injury, which is involved in the protective effect of ischemic preconditioning (..
  28. Gq-coupled Receptors Inhibit PI 3-kinase/Akt Signaling Pathway
    Richard Z Lin; Fiscal Year: 2010
    The goal of this proposal is to understand the role of class IA phosphatidylinositol 3-kinase (PI3K) p110a and p110 in regulating pathological and physiological cell growth in the pancreas and skeletal muscle...
  29. Gq-coupled Receptors Inhibit PI 3-kinase/Akt Signaling Pathway
    Richard Z Lin; Fiscal Year: 2010
    The goal of this proposal is to understand the role of class IA phosphatidylinositol 3-kinase (PI3K) p110a and p110 in regulating pathological and physiological cell growth in the pancreas and skeletal muscle...
  30. TPN INDUCED CHANGES IN INTRAEPITHELIAL LYMPHOCYTES
    Daniel H Teitelbaum; Fiscal Year: 2010
    ..These cytokine changes may well be key mechanisms leading to the loss of EBF, and appears to be regulated via the PI3K/p-Akt signaling pathway...
  31. NF-KB and mTOR regulation in Waldenstrom Macroglobulinemia
    Irene M Ghobrial; Fiscal Year: 2010
    ..The PI3K/mTOR and NF-kB pathways act as critical regulators of apoptosis, cell cycle, and tumor proliferation in ..
  32. Integrin-collagen signaling and control of fibroblast proliferation
    Craig A Henke; Fiscal Year: 2010
    ..as a tumor suppressor by negatively regulating proliferation by repressing the integrin-phosphoinositol 3-kinase (PI3K)/Akt signaling pathway...
  33. Targeting PI3K/Akt Cell Survival Pathway as a Novel Anti-HIV Therapy
    Baek Kim; Fiscal Year: 2010
    ..Our preliminary data also suggest that the well characterized PI3K/Akt survival pathway is mechanistically involved in the cytoprotective effect of HIV-1 infection and intracellular ..
  34. Novel regulation of beta-adrenergic receptor function by phosphoinositide 3-kinas
    SATHYAMANGLA PRASAD; Fiscal Year: 2009
    ..Previously we have shown that bARK1 interacts with phosphoinositide 3-kinase (PI3K) to form a cytosolic complex targeting PI3K to the activated receptor where PI3K plays a role in receptor ..
  35. Novel regulation of beta-adrenergic receptor function by phosphoinositide 3-kinas
    SATHYAMANGLA VENKATA PRASAD; Fiscal Year: 2010
    ..Previously we have shown that bARK1 interacts with phosphoinositide 3-kinase (PI3K) to form a cytosolic complex targeting PI3K to the activated receptor where PI3K plays a role in receptor ..
  36. Inhibition of P13k and MEK Pathways in the Treatment of Lung Cancer
    KWOK KIN contact WONG; Fiscal Year: 2010
    ..unique in that the critical intracellular survival and growth signaling pathways such as phosphoinositide 3-kinase (PI3K) and extracellular signal-regulated kinase (ERK) are solely regulated by EGFR...
  37. Cell Volume Regulated Biology in the Liver
    Ravi Chari; Fiscal Year: 2005
    ..Preliminary data from our lab has [sic] demonstrated activation of MAPKinases and PI3K with induction of transcription factors AP-1 and NF-KB following aniso-osmotic induced cell swelling in Hep G2 ..
  38. RGS: A Molecular Switch Regulating Irreversible ASM Growth/Contraction in Asthma
    Reynold Panettieri; Fiscal Year: 2009
    ..Growth factors require activation of Src, phosphatidylinositol 3-kinase (PI3K) and S6K1 to stimulate ASM growth...
  39. RGS: A Molecular Switch Regulating Irreversible ASM Growth/Contraction in Asthma
    REYNOLD ALEXANDER PANETTIERI; Fiscal Year: 2010
    ..Growth factors require activation of Src, phosphatidylinositol 3-kinase (PI3K) and S6K1 to stimulate ASM growth...