Genomes and Genes
protein serine threonine kinases
Summary: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
- Iwahashi M, Katsuda M, Nakamori M, Nakamura M, Naka T, Ojima T, et al. Vaccination with peptides derived from cancer-testis antigens in combination with CpG-7909 elicits strong specific CD8+ T cell response in patients with metastatic esophageal squamous cell carcinoma. Cancer Sci. 2010;101:2510-7 pubmed publisher..This vaccine protocol is therefore recommended to undergo further phase II trials. ..
- Dzamko N, Deak M, Hentati F, Reith A, Prescott A, Alessi D, et al. Inhibition of LRRK2 kinase activity leads to dephosphorylation of Ser(910)/Ser(935), disruption of 14-3-3 binding and altered cytoplasmic localization. Biochem J. 2010;430:405-13 pubmed publisher..They will also stimulate further research to understand how phosphorylation of Ser910 and Ser935 is controlled by LRRK2, and establish any relationship to development of Parkinson's disease. ..
- Gehrke S, Imai Y, SOKOL N, Lu B. Pathogenic LRRK2 negatively regulates microRNA-mediated translational repression. Nature. 2010;466:637-41 pubmed publisher..Our results implicate deregulated synthesis of E2F1/DP caused by the miRNA pathway impairment as a key event in LRRK2 pathogenesis and suggest novel miRNA-based therapeutic strategies. ..
- Ren H, Zhang H. Wnt signaling controls temporal identities of seam cells in Caenorhabditis elegans. Dev Biol. 2010;345:144-55 pubmed publisher..Our study reveals a novel function of Wnt signaling in controlling the timing of seam cell development in C. elegans. ..
- Kanu N, Penicud K, Hristova M, Wong B, Irvine E, Plattner F, et al. The ATM cofactor ATMIN protects against oxidative stress and accumulation of DNA damage in the aging brain. J Biol Chem. 2010;285:38534-42 pubmed publisher..These results suggest that ATMIN mediates ATM activation by oxidative stress, and thereby ATMIN protects the aging brain by preventing accumulation of DNA damage. ..
- Sari F, Watanabe K, Widyantoro B, Thandavarayan R, Harima M, Zhang S, et al. Partial inactivation of cardiac 14-3-3 protein in vivo elicits endoplasmic reticulum stress (ERS) and activates ERS-initiated apoptosis in ERS-induced mice. Cell Physiol Biochem. 2010;26:167-78 pubmed publisher..The enhancement of 14-3-3 protein may provide a novel protective therapy against cardiac ERS and ERS-initiated apoptosis, at least in part, through the regulation of CHOP and caspase-12 via the Ire1alpha/TRAF2 pathway. ..
- Nalapareddy K, Choudhury A, Gompf A, Ju Z, Ravipati S, Leucht T, et al. CHK2-independent induction of telomere dysfunction checkpoints in stem and progenitor cells. EMBO Rep. 2010;11:619-25 pubmed publisher..Together, these results indicate that CHK2 mediates the induction of senescence in fibroblasts, but is dispensable for the induction of telomere dysfunction checkpoints at the stem and progenitor cell level in vivo. ..
- Di Fiore B, Pines J. How cyclin A destruction escapes the spindle assembly checkpoint. J Cell Biol. 2010;190:501-9 pubmed publisher..Subsequently, the Cks protein is necessary and sufficient to promote cyclin A degradation in the presence of an active checkpoint by binding cyclin A-Cdc20 to the APC/C. ..
- Han H, Zhong C, Zhang X, Liu R, Pan M, Tan L, et al. Genistein induces growth inhibition and G2/M arrest in nasopharyngeal carcinoma cells. Nutr Cancer. 2010;62:641-7 pubmed publisher..Moreover, selective estrogen receptor modulators did not affect genistein induced growth inhibition. These findings provide new insights into the potential intervention of NPC with genistein. ..
- Yang L, Qiao G, Ying H, Zhang J, Yin F. TCR-induced Akt serine 473 phosphorylation is regulated by protein kinase C-alpha. Biochem Biophys Res Commun. 2010;400:16-20 pubmed publisher..Knockdown of PKC-alpha in T-cell-line Jurkat cells reduced TCR-induced phosphorylation of Akt as well as its downstream targets. Thus our results suggest that PKC-alpha is a candidate for PDK-2 in T cells upon TCR stimulation. ..
- Wang H, Ryu W. Hepatitis B virus polymerase blocks pattern recognition receptor signaling via interaction with DDX3: implications for immune evasion. PLoS Pathog. 2010;6:e1000986 pubmed publisher..A therapeutic implication of this work is that a strategy to interfere with the HBV Pol-DDX3 interaction might lead to the resolution of life-long persistent infection...
- Mortier J, Masereel B, Remouchamps C, Ganeff C, Piette J, Frederick R. NF-kappaB inducing kinase (NIK) inhibitors: identification of new scaffolds using virtual screening. Bioorg Med Chem Lett. 2010;20:4515-20 pubmed publisher..This study opens new perspectives in the field of the NF-kappaB alternative pathway inhibition. ..
- Li X, Fan Z. The epidermal growth factor receptor antibody cetuximab induces autophagy in cancer cells by downregulating HIF-1alpha and Bcl-2 and activating the beclin 1/hVps34 complex. Cancer Res. 2010;70:5942-52 pubmed publisher..Our findings suggest that the autophagy protects cancer cells from the proapoptotic effects of cetuximab. ..
- Strudwick N, Brown M, Parmar V, Schroder M. Ime1 and Ime2 are required for pseudohyphal growth of Saccharomyces cerevisiae on nonfermentable carbon sources. Mol Cell Biol. 2010;30:5514-30 pubmed publisher..Based on these findings, we propose to include exit from pseudohyphal growth and entry into meiosis in the life cycle of S. cerevisiae. ..
- Menichincheri M, Albanese C, Alli C, Ballinari D, Bargiotti A, Caldarelli M, et al. Cdc7 kinase inhibitors: 5-heteroaryl-3-carboxamido-2-aryl pyrroles as potential antitumor agents. 1. Lead finding. J Med Chem. 2010;53:7296-315 pubmed publisher..Derivative 18 represents a new lead compound worthy of further investigation toward the ultimate goal of identifying a clinical candidate. ..
- Wu S, Zhang Y, Tao H, Dong L. Lipoxin A(4) inhibits transition of epithelial to mesenchymal cells in proximal tubules. Am J Nephrol. 2010;32:122-36 pubmed publisher..LXA(4) inhibits the tubular epithelial to mesenchymal transition, initiated by CTGF but not by TGF-beta(1), via downregulation of ILK, Ras/MEK/ERK1/2 and PI3-K/Akt-dependent signal pathway stimulated by CTGF. ..
- Schayowitz A, Sabnis G, Goloubeva O, Njar V, Brodie A. Prolonging hormone sensitivity in prostate cancer xenografts through dual inhibition of AR and mTOR. Br J Cancer. 2010;103:1001-7 pubmed publisher..Furthermore, after bicalutamide failure, dual inhibition with VN/124-1 and everolimus was the most effective treatment. ..
- Nemoto N, Udagawa T, Ohira T, Jiang L, Hirota K, Wilkinson C, et al. The roles of stress-activated Sty1 and Gcn2 kinases and of the protooncoprotein homologue Int6/eIF3e in responses to endogenous oxidative stress during histidine starvation. J Mol Biol. 2010;404:183-201 pubmed publisher..These results suggest that Gcn2, Sty1, and Int6/eIF3e are functionally integrated and cooperate to respond to oxidative stress generated during histidine starvation. ..
- Rao V, Klein S, Bonar S, Zielonka J, Mizuno N, Dickey J, et al. The antioxidant transcription factor Nrf2 negatively regulates autophagy and growth arrest induced by the anticancer redox agent mitoquinone. J Biol Chem. 2010;285:34447-59 pubmed publisher..Keap1 and Nrf2 act as redox sensors for oxidative perturbations that lead to autophagy. MitoQ and similar compounds should be further evaluated for novel anticancer activity. ..
- Hurov K, Cotta Ramusino C, Elledge S. A genetic screen identifies the Triple T complex required for DNA damage signaling and ATM and ATR stability. Genes Dev. 2010;24:1939-50 pubmed publisher..The components of the TTT complex are mutually dependent on each other, and act as critical regulators of PIKK abundance and checkpoint signaling. ..
- Karpowicz P, Perez J, Perrimon N. The Hippo tumor suppressor pathway regulates intestinal stem cell regeneration. Development. 2010;137:4135-45 pubmed publisher..These findings demonstrate a cell-autonomous role for the Hippo pathway in SCs, and have implications for understanding the role of this pathway in tumorigenesis and cancer stem cells. ..
- Dudgeon D, Shinde S, Shun T, Lazo J, Strock C, Giuliano K, et al. Characterization and optimization of a novel protein-protein interaction biosensor high-content screening assay to identify disruptors of the interactions between p53 and hDM2. Assay Drug Dev Technol. 2010;8:437-58 pubmed publisher..Further, their corresponding cellular images and quantitative HCS data did not completely match the Nutlin-3 phenotypic profile. ..
- Ross O, Wilhoite G, Bacon J, Soto Ortolaza A, Kachergus J, Cobb S, et al. LRRK2 variation and Parkinson's disease in African Americans. Mov Disord. 2010;25:1973-6 pubmed publisher..Given the ethnic-specific LRRK2 variation previously identified in PD further studies in under-represented populations are warranted. ..
- Huang M, Kim J, Shiotani B, Yang K, Zou L, D Andrea A. The FANCM/FAAP24 complex is required for the DNA interstrand crosslink-induced checkpoint response. Mol Cell. 2010;39:259-68 pubmed publisher..Therefore, we propose that FANCM/FAAP24 plays a role in ICL-induced checkpoint activation through regulating RPA recruiment at ICL-stalled replication forks. ..
- Ohouo P, Bastos de Oliveira F, Almeida B, Smolka M. DNA damage signaling recruits the Rtt107-Slx4 scaffolds via Dpb11 to mediate replication stress response. Mol Cell. 2010;39:300-6 pubmed publisher..Our results unveil how Mec1 regulates the Slx4 and Rtt107 scaffolds and establish a mechanistic link between DNA damage signaling and fork repair. ..
- Porcu G, Wilson C, Di Giandomenico D, Ragnini Wilson A. A yeast-based genomic strategy highlights the cell protein networks altered by FTase inhibitor peptidomimetics. Mol Cancer. 2010;9:197 pubmed publisher..Moreover, it stresses the importance of monitoring the MDR response in patients treated with FTIs. ..
- Li X, Moore D, Xiong Y, Dawson T, Dawson V. Reevaluation of phosphorylation sites in the Parkinson disease-associated leucine-rich repeat kinase 2. J Biol Chem. 2010;285:29569-76 pubmed publisher..Using these antibodies, we have found that all three putative sites are phosphorylated in LRRK2, and Ser-2032 and Thr-2035 are the two important sites that regulate LRRK2 kinase activity. ..
- Bandyopadhyay S, Mehta M, Kuo D, Sung M, Chuang R, Jaehnig E, et al. Rewiring of genetic networks in response to DNA damage. Science. 2010;330:1385-9 pubmed publisher..Differential networks chart a new type of genetic landscape that is invaluable for mapping cellular responses to stimuli. ..
- Berthon C, Driss V, Liu J, Kuranda K, Leleu X, Jouy N, et al. In acute myeloid leukemia, B7-H1 (PD-L1) protection of blasts from cytotoxic T cells is induced by TLR ligands and interferon-gamma and can be reversed using MEK inhibitors. Cancer Immunol Immunother. 2010;59:1839-49 pubmed publisher..The efficacy of MEK inhibitors against B7-H1-mediated inhibition of CTLs suggests a possible cancer immunotherapy strategy using targeted drugs. ..
- Martínez López N, Varela Rey M, Fernandez Ramos D, Woodhoo A, Vazquez Chantada M, Embade N, et al. Activation of LKB1-Akt pathway independent of phosphoinositide 3-kinase plays a critical role in the proliferation of hepatocellular carcinoma from nonalcoholic steatohepatitis. Hepatology. 2010;52:1621-31 pubmed publisher..The SAMe-D cell line is a relevant model of HCC derived from NASH disease in which LKB1 is the principal conductor of a new regulatory mechanism and could be a practical tool for uncovering new therapeutic strategies. ..
- Cluzel M, Zanella Cleon I, Cozzone A, Futterer K, Duclos B, Molle V. The Staphylococcus aureus autoinducer-2 synthase LuxS is regulated by Ser/Thr phosphorylation. J Bacteriol. 2010;192:6295-301 pubmed publisher..aureus possesses an original and specific system for controlling AI-2 synthesis. ..
- Ren K, Duan W, Shi Y, Li B, Liu Z, Gong J. Ectopic over-expression of oncogene Pim-2 induce malignant transformation of nontumorous human liver cell line L02. J Korean Med Sci. 2010;25:1017-23 pubmed publisher..L02/Pim-2 cells could generate hepatoma in athymic mice. In conclusion, Pim-2 could induce malignant transformation of human liver cell line L02. ..
- Giunta S, Belotserkovskaya R, Jackson S. DNA damage signaling in response to double-strand breaks during mitosis. J Cell Biol. 2010;190:197-207 pubmed publisher..Finally, we present data suggesting that induction of a primary DDR in mitosis is important because transient inactivation of ATM and DNA-PK renders mitotic cells hypersensitive to DSB-inducing agents. ..
- Kiilerich K, Adser H, Jakobsen A, Pedersen P, Hardie D, Wojtaszewski J, et al. PGC-1alpha increases PDH content but does not change acute PDH regulation in mouse skeletal muscle. Am J Physiol Regul Integr Comp Physiol. 2010;299:R1350-9 pubmed publisher..In conclusion, PGC-1? regulates PDH-E1? protein content in parallel with mitochondrial oxidative proteins, but does not seem to influence PDH regulation in mouse skeletal muscle in response to fasting and in recovery from exercise. ..
- Huntoon C, Nye M, Geng L, Peterson K, Flatten K, Haluska P, et al. Heat shock protein 90 inhibition depletes LATS1 and LATS2, two regulators of the mammalian hippo tumor suppressor pathway. Cancer Res. 2010;70:8642-50 pubmed publisher..Taken together, these results identify LATS1 and LATS2 as novel HSP90 clients and show that HSP90 inhibitors can disrupt the LATS tumor suppressor pathway in human cancer cells. ..
- Liew C, Bochenski J, Kawamori D, Hu J, Leech C, Wanic K, et al. The pseudokinase tribbles homolog 3 interacts with ATF4 to negatively regulate insulin exocytosis in human and mouse beta cells. J Clin Invest. 2010;120:2876-88 pubmed publisher..These data link a missense polymorphism in human TRB3 to impaired insulin exocytosis and thus increased risk for T2DM. ..
- Gupta S, Deepti A, Deegan S, Lisbona F, Hetz C, Samali A. HSP72 protects cells from ER stress-induced apoptosis via enhancement of IRE1alpha-XBP1 signaling through a physical interaction. PLoS Biol. 2010;8:e1000410 pubmed publisher..Our data show that binding of Hsp72 to IRE1alpha enhances IRE1alpha/XBP1 signaling at the ER and inhibits ER stress-induced apoptosis. These results provide a physical connection between cytosolic chaperones and the ER stress response. ..
- Furgeson S, Linas S. Mechanisms of type I and type II pseudohypoaldosteronism. J Am Soc Nephrol. 2010;21:1842-5 pubmed publisher..WNK1 also regulates NCC and ROMK. Aldosterone inactivates WNK1 and WNK4 activity. Whether angiotensin II can fine tune the actions of aldosterone is still unclear...
- Lipsitz E, Moorthy G, Mosse Y, Fox E, Adamson P. A sensitive and selective liquid chromatography/tandem mass spectrometry method for determination of MLN8237 in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2010;878:2369-73 pubmed publisher..The analytical method showed excellent sensitivity, precision, and accuracy. This method is robust and is being successfully employed in a Children's Oncology Group Phase 1 Consortium study of MLN8237 in children with cancer. ..
- Bianchini G, Qi Y, Alvarez R, Iwamoto T, Coutant C, Ibrahim N, et al. Molecular anatomy of breast cancer stroma and its prognostic value in estrogen receptor-positive and -negative cancers. J Clin Oncol. 2010;28:4316-23 pubmed publisher..Other stromal metagenes had inconsistent prognostic value. Among ER-negative and ER-positive highly proliferative cancers, a subset of tumors with high expression of a B-cell/plasma cell metagene carries a favorable prognosis. ..
- Jha K, Wong L, Zerfas P, De Silva R, Fan Y, Spiridonov N, et al. Identification of a novel HSP70-binding cochaperone critical to HSP90-mediated activation of small serine/threonine kinase. J Biol Chem. 2010;285:35180-7 pubmed publisher..Hence, these findings demonstrate that HSP90 is essential for functional maturation of the kinase and identify SIP as a cochaperone that is critical to the HSP90-mediated activation of SSTK...
- Niu G, Ji Y, Jin D, Hou J, Lou W. [Clinical implication of BRSK2 expression in pancreatic ductal adenocarcinoma]. Zhonghua Yi Xue Za Zhi. 2010;90:1084-8 pubmed..Those with a higher expression pattern showed a shorter survival period. BRSK2 is up-regulated in pancreatic ductal adenocarcinoma. And its expression is correlated with tumor biological behaviors and patient prognosis. ..
- Argani P, Hicks J, De Marzo A, Albadine R, Illei P, Ladanyi M, et al. Xp11 translocation renal cell carcinoma (RCC): extended immunohistochemical profile emphasizing novel RCC markers. Am J Surg Pathol. 2010;34:1295-303 pubmed publisher..Elevated expression of phosphorylated S6 in Xp11 translocation RCC suggests the mTOR pathway as an attractive potential therapeutic target for these neoplasms...
- Yang S, Lo Y, Wu C, Lin S, Yeh C, Chu P, et al. SPAK-knockout mice manifest Gitelman syndrome and impaired vasoconstriction. J Am Soc Nephrol. 2010;21:1868-77 pubmed publisher..In summary, SPAK-null mice have defects of NCC in the kidneys and NKCC1 in the blood vessels, leading to hypotension through renal salt wasting and vasodilation. SPAK may be a promising target for antihypertensive therapy...
- Tomsic J, Guda K, Liyanarachchi S, Hampel H, Natale L, Markowitz S, et al. Allele-specific expression of TGFBR1 in colon cancer patients. Carcinogenesis. 2010;31:1800-4 pubmed publisher..More advanced technology is expected to resolve this issue as well as the low informativity caused by the limited heterozygosity of transcribed SNPs. ..
- Miura Y, Endo T. Survival responses to oxidative stress and aging. Geriatr Gerontol Int. 2010;10 Suppl 1:S1-9 pubmed publisher..This review will focus on the repair and adaptive response to oxidative stress, and summarize the changes of these systems as a result aging and their relationship to premature aging. ..
- Wu F, Saleem M, Kampik N, Satchwell T, Williamson R, Blattner S, et al. Anion exchanger 1 interacts with nephrin in podocytes. J Am Soc Nephrol. 2010;21:1456-67 pubmed publisher..These data suggest that the podocyte protein kAE1 interacts with nephrin and ILK to maintain the structure and function of the glomerular basement membrane. ..
- Matsuo K, Nishimura T, Hayakawa A, Ono Y, Takahashi M. Involvement of a centrosomal protein kendrin in the maintenance of centrosome cohesion by modulating Nek2A kinase activity. Biochem Biophys Res Commun. 2010;398:217-23 pubmed publisher..Taken together, these results suggest that kendrin anchors Nek2A and suppresses its kinase activity at the centrosomes, and thus, is involved in the mechanism to prevent premature centrosome splitting during interphase. ..