Pik3cg

Summary

Gene Symbol: Pik3cg
Description: phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma
Alias: 5830428L06Rik, PI3Kgamma, p110gamma, phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform, PI3-kinase subunit gamma, PI3K-gamma, p120-PI3K, phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit gamma, phosphoinositide-3-kinase, catalytic, gamma polypeptide, ptdIns-3-kinase subunit gamma, ptdIns-3-kinase subunit p110-gamma, serine/threonine protein kinase PIK3CG
Species: mouse
Products:     Pik3cg

Top Publications

  1. Reif K, Okkenhaug K, Sasaki T, Penninger J, Vanhaesebroeck B, Cyster J. Cutting edge: differential roles for phosphoinositide 3-kinases, p110gamma and p110delta, in lymphocyte chemotaxis and homing. J Immunol. 2004;173:2236-40 pubmed
    ..In this study, we report that p110gamma-deficient T cells, but not B cells, show reduced chemotactic responses to the lymphoid chemokines, CCL19, CCL21, ..
  2. Kerfant B, Zhao D, Lorenzen Schmidt I, Wilson L, Cai S, Chen S, et al. PI3Kgamma is required for PDE4, not PDE3, activity in subcellular microdomains containing the sarcoplasmic reticular calcium ATPase in cardiomyocytes. Circ Res. 2007;101:400-8 pubmed
    We recently showed that phosphoinositide-3-kinase-gamma-deficient (PI3Kgamma(-/-)) mice have enhanced cardiac contractility attributable to cAMP-dependent increases in sarcoplasmic reticulum (SR) Ca(2+) content and release but not L-type ..
  3. Alcázar I, Marqués M, Kumar A, Hirsch E, Wymann M, Carrera A, et al. Phosphoinositide 3-kinase gamma participates in T cell receptor-induced T cell activation. J Exp Med. 2007;204:2977-87 pubmed
    ..divided into two types: class I(A) p85/p110 heterodimers, which are activated by Tyr kinases, and the class I(B) p110gamma isoform, which is activated by GPCR...
  4. Jin R, Song Z, Yu S, Piazza A, Nanda A, Penninger J, et al. Phosphatidylinositol-3-kinase gamma plays a central role in blood-brain barrier dysfunction in acute experimental stroke. Stroke. 2011;42:2033-44 pubmed publisher
    ..Future studies need to explore PI3K? as a potential target for stroke therapy. ..
  5. Crackower M, Oudit G, Kozieradzki I, Sarao R, Sun H, Sasaki T, et al. Regulation of myocardial contractility and cell size by distinct PI3K-PTEN signaling pathways. Cell. 2002;110:737-49 pubmed
    ..PI3Kalpha mediates the alteration in cell size while PI3Kgamma acts as a negative regulator of cardiac contractility...
  6. Li Z, Jiang H, Xie W, Zhang Z, Smrcka A, Wu D. Roles of PLC-beta2 and -beta3 and PI3Kgamma in chemoattractant-mediated signal transduction. Science. 2000;287:1046-9 pubmed
    ..b>PI3Kgamma was required for chemoattractant-induced production of phosphatidylinositol 3,4,5-trisphosphate [PtdIns (3,4,5)..
  7. Sasaki T, Irie Sasaki J, Horie Y, Bachmaier K, Fata J, Li M, et al. Colorectal carcinomas in mice lacking the catalytic subunit of PI(3)Kgamma. Nature. 2000;406:897-902 pubmed
    ..Here we report that genetic inactivation of the p110gamma catalytic subunit of PI(3)Kgamma (ref. 8) leads to development of invasive colorectal adenocarcinomas in mice...
  8. Bohnacker T, Marone R, Collmann E, Calvez R, Hirsch E, Wymann M. PI3Kgamma adaptor subunits define coupling to degranulation and cell motility by distinct PtdIns(3,4,5)P3 pools in mast cells. Sci Signal. 2009;2:ra27 pubmed publisher
    ..It is a heterodimer of a catalytic p110gamma subunit and an adaptor protein, either p101 or the p101 homolog p84 (p87(PIKAP))...
  9. Smith D, Deem T, Bruce A, Reutershan J, Wu D, Ley K. Leukocyte phosphoinositide-3 kinase {gamma} is required for chemokine-induced, sustained adhesion under flow in vivo. J Leukoc Biol. 2006;80:1491-9 pubmed
    ..We conclude that the gamma isoform of PI-3K must be functional in leukocytes to allow efficient adhesion from rolling in response to chemokine stimulation. ..

More Information

Publications74

  1. Jones G, Prigmore E, Calvez R, Hogan C, Dunn G, Hirsch E, et al. Requirement for PI 3-kinase gamma in macrophage migration to MCP-1 and CSF-1. Exp Cell Res. 2003;290:120-31 pubmed
    ..Here, we investigate the contribution of PI3Kgamma to macrophage responses to chemoattractants, using bone marrow-derived macrophages from wild-type and PI3Kgamma-..
  2. Schmidt C, Schneble N, Muller J, Bauer R, Perino A, Marone R, et al. Phosphoinositide 3-kinase ? mediates microglial phagocytosis via lipid kinase-independent control of cAMP. Neuroscience. 2013;233:44-53 pubmed publisher
    ..In sum our findings indicate PI3K?-dependent suppression of cAMP signaling as a critical regulatory element of microglial phagocytosis. ..
  3. Nishio M, Watanabe K, Sasaki J, Taya C, Takasuga S, Iizuka R, et al. Control of cell polarity and motility by the PtdIns(3,4,5)P3 phosphatase SHIP1. Nat Cell Biol. 2007;9:36-44 pubmed
    ..By directing where PtdIns(3,4,5)P(3) accumulates, SHIP1 governs the formation of the leading edge and polarization required for chemotaxis. ..
  4. Takeda M, Ito W, Tanabe M, Ueki S, Kato H, Kihara J, et al. Allergic airway hyperresponsiveness, inflammation, and remodeling do not develop in phosphoinositide 3-kinase gamma-deficient mice. J Allergy Clin Immunol. 2009;123:805-12 pubmed publisher
    ..of the involvement between the pathogenesis of asthma and PI3K have been performed, it is unknown whether PI3Kgamma, a PI3K isoform, is involved in the pathogenesis of asthma...
  5. Fougerat A, Gayral S, Gourdy P, Schambourg A, Ruckle T, Schwarz M, et al. Genetic and pharmacological targeting of phosphoinositide 3-kinase-gamma reduces atherosclerosis and favors plaque stability by modulating inflammatory processes. Circulation. 2008;117:1310-7 pubmed publisher
    ..The lipid kinase phosphoinositide 3-kinase-gamma (PI3Kgamma) is thought to be a key player in various inflammatory, autoimmune, and allergic processes...
  6. Curcio A, Noma T, Naga Prasad S, Wolf M, Lemaire A, Perrino C, et al. Competitive displacement of phosphoinositide 3-kinase from beta-adrenergic receptor kinase-1 improves postinfarction adverse myocardial remodeling. Am J Physiol Heart Circ Physiol. 2006;291:H1754-60 pubmed
    ..Together, these results demonstrate that adverse remodeling of the ventricle after MI can be attenuated by a strategy that prevents recruitment of PI3K to the plasma membrane and restores normal beta-AR function. ..
  7. Castor M, Rezende B, Bernardes P, Vieira A, Vieira E, Arantes R, et al. PI3K? controls leukocyte recruitment, tissue injury, and lethality in a model of graft-versus-host disease in mice. J Leukoc Biol. 2011;89:955-64 pubmed publisher
    ..In conclusion, PI(3)K? plays a critical role in GVHD by mediating leukocyte influx and activation in tissues. PI(3)K? inhibitors may be useful in the treatment of GVHD in patients undergoing BMT. ..
  8. Harris S, Ciuclan L, Finan P, Wymann M, Walker C, Westwick J, et al. Genetic ablation of PI3K? results in defective IL-17RA signalling in T lymphocytes and increased IL-17 levels. Eur J Immunol. 2012;42:3394-404 pubmed publisher
    ..Cell influx in response to IL-17 was also reduced in PI3K?(-/-) lungs. These data demonstrate PI3K?-dependent signalling downstream of IL-17RA, which plays a pivotal role in regulating IL-17 production in T cells. ..
  9. Beer Hammer S, Zebedin E, von Holleben M, Alferink J, Reis B, Dresing P, et al. The catalytic PI3K isoforms p110gamma and p110delta contribute to B cell development and maintenance, transformation, and proliferation. J Leukoc Biol. 2010;87:1083-95 pubmed publisher
    ..of gene-deficient mice revealed specific roles for the hematopoietically expressed PI3K catalytic subunits, p110gamma and p110delta, in development and function of T and B lymphocytes...
  10. Rodrigues D, Vilela M, Barcelos L, Pinho V, Teixeira M, Teixeira A. Absence of PI3Kgamma leads to increased leukocyte apoptosis and diminished severity of experimental autoimmune encephalomyelitis. J Neuroimmunol. 2010;222:90-4 pubmed publisher
    Phosphatidylinositol-3-kinase gamma (PI3Kgamma) plays an important role in the motility of leukocytes in several models of inflammation...
  11. Konig C, Gavrilova Ruch O, von Banchet G, Bauer R, Grun M, Hirsch E, et al. Modulation of mu opioid receptor desensitization in peripheral sensory neurons by phosphoinositide 3-kinase gamma. Neuroscience. 2010;169:449-54 pubmed publisher
    ..Here we document a specific role of the G protein-coupled class IB isoform PI3Kgamma in MOR desensitization in mice and isolated sensory neurons...
  12. Foukas L, Berenjeno I, Gray A, Khwaja A, Vanhaesebroeck B. Activity of any class IA PI3K isoform can sustain cell proliferation and survival. Proc Natl Acad Sci U S A. 2010;107:11381-6 pubmed publisher
    ..of either p110alpha or p110delta did not affect cell proliferation or survival or sensitize to p110beta or p110gamma inactivation...
  13. Laffargue M, Calvez R, Finan P, Trifilieff A, Barbier M, Altruda F, et al. Phosphoinositide 3-kinase gamma is an essential amplifier of mast cell function. Immunity. 2002;16:441-51 pubmed
    ..signals through G protein-coupled receptors (GPCRs) and require functional phosphoinositide 3-kinase gamma (PI3Kgamma)...
  14. Kobayashi N, Ueki K, Okazaki Y, Iwane A, Kubota N, Ohsugi M, et al. Blockade of class IB phosphoinositide-3 kinase ameliorates obesity-induced inflammation and insulin resistance. Proc Natl Acad Sci U S A. 2011;108:5753-8 pubmed publisher
    ..Mice lacking p110? (Pik3cg(-/-)), the catalytic subunit of PI3K?, exhibited improved systemic insulin sensitivity with enhanced insulin ..
  15. Guillermet Guibert J, Bjorklof K, Salpekar A, Gonella C, Ramadani F, Bilancio A, et al. The p110beta isoform of phosphoinositide 3-kinase signals downstream of G protein-coupled receptors and is functionally redundant with p110gamma. Proc Natl Acad Sci U S A. 2008;105:8292-7 pubmed publisher
    ..The p84/p101 regulatory subunits of the p110gamma class IB PI3K lack SH2 domains and instead couple p110gamma to G protein-coupled receptors (GPCRs)...
  16. Yago T, Shao B, Miner J, Yao L, Klopocki A, Maeda K, et al. E-selectin engages PSGL-1 and CD44 through a common signaling pathway to induce integrin alphaLbeta2-mediated slow leukocyte rolling. Blood. 2010;116:485-94 pubmed publisher
    ..Thus, E-selectin triggers common signals through distinct neutrophil glycoproteins to induce alpha(L)beta(2)-dependent slow rolling. ..
  17. Zhao M, Song B, Pu J, Wada T, Reid B, Tai G, et al. Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN. Nature. 2006;442:457-60 pubmed
    ..These data identify genes essential for electrical-signal-induced wound healing and show that PI(3)Kgamma and PTEN control electrotaxis. ..
  18. Ban K, Cooper A, Samuel S, Bhatti A, Patel M, Izumo S, et al. Phosphatidylinositol 3-kinase gamma is a critical mediator of myocardial ischemic and adenosine-mediated preconditioning. Circ Res. 2008;103:643-53 pubmed publisher
    ..We demonstrate the selective role of phosphatidylinositol 3-kinase (PI3K) isoforms in IPC. Hearts from PI3Kgamma knockout mice (PI3Kgamma(-/-)) displayed poorer functional recovery and greater tissue injury following IPC ..
  19. Kim J, Lee H, Sim S, Baek J, Yu N, Choi J, et al. PI3K? is required for NMDA receptor-dependent long-term depression and behavioral flexibility. Nat Neurosci. 2011;14:1447-54 pubmed publisher
    ..Thus, individual isoforms of PI3Ks may have distinct roles in different types of synaptic plasticity and may therefore influence various kinds of behavior. ..
  20. Hirsch E, Katanaev V, Garlanda C, Azzolino O, Pirola L, Silengo L, et al. Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation. Science. 2000;287:1049-53 pubmed
    ..Mice lacking heterotrimeric guanine nucleotide-binding protein (G protein)-coupled PI3Kgamma were viable and had fully differentiated neutrophils and macrophages...
  21. MacDonald P, Joseph J, Yau D, Diao J, Asghar Z, Dai F, et al. Impaired glucose-stimulated insulin secretion, enhanced intraperitoneal insulin tolerance, and increased beta-cell mass in mice lacking the p110gamma isoform of phosphoinositide 3-kinase. Endocrinology. 2004;145:4078-83 pubmed
    ..The G protein-activated p110gamma isoform of PI3 kinase was detected in insulinoma cells, mouse islets, and human islets...
  22. Hayer S, Pundt N, Peters M, Wunrau C, Kühnel I, Neugebauer K, et al. PI3Kgamma regulates cartilage damage in chronic inflammatory arthritis. FASEB J. 2009;23:4288-98 pubmed publisher
    The gamma isoform of phosphoinositide 3-kinase (PI3Kgamma) has been viewed as restricted to leukocytes mediating the regulation of chemokine-induced migration and recruitment of neutrophils, monocytes, and macrophages...
  23. van Dop W, Marengo S, te Velde A, Ciraolo E, Franco I, ten Kate F, et al. The absence of functional PI3Kgamma prevents leukocyte recruitment and ameliorates DSS-induced colitis in mice. Immunol Lett. 2010;131:33-9 pubmed publisher
    Phosphatidylinositol-3-kinase gamma (PI3Kgamma) is the major PI3K that is activated in response to chemoattractants. It is responsible for the migration of leukocytes from the bloodstream to sites of injury or infection...
  24. Kulkarni S, Sitaru C, Jakus Z, Anderson K, Damoulakis G, Davidson K, et al. PI3Kβ plays a critical role in neutrophil activation by immune complexes. Sci Signal. 2011;4:ra23 pubmed publisher
    ..These results define PI3Kβ as a potential therapeutic target in inflammatory disease. ..
  25. Ghigo A, Perino A, Mehel H, Zahradnikova A, Morello F, Leroy J, et al. Phosphoinositide 3-kinase ? protects against catecholamine-induced ventricular arrhythmia through protein kinase A-mediated regulation of distinct phosphodiesterases. Circulation. 2012;126:2073-83 pubmed publisher
    ..PI3K? coordinates the coincident signaling of the major cardiac PDE3 and PDE4 isoforms, thus orchestrating a feedback loop that prevents calcium-dependent ventricular arrhythmia. ..
  26. Nombela Arrieta C, Mempel T, Soriano S, Mazo I, Wymann M, Hirsch E, et al. A central role for DOCK2 during interstitial lymphocyte motility and sphingosine-1-phosphate-mediated egress. J Exp Med. 2007;204:497-510 pubmed
    ..T and B cells lacking DOCK2 alone or DOCK2 and PI3Kgamma displayed markedly reduced motility inside T cell area and B cell follicle, respectively...
  27. Becattini B, Marone R, Zani F, Arsenijevic D, Seydoux J, Montani J, et al. PI3K? within a nonhematopoietic cell type negatively regulates diet-induced thermogenesis and promotes obesity and insulin resistance. Proc Natl Acad Sci U S A. 2011;108:E854-63 pubmed publisher
    ..Thus, PI3K? is an unexpected but promising drug target for the treatment of obesity and its complications. ..
  28. Heit B, Liu L, Colarusso P, Puri K, Kubes P. PI3K accelerates, but is not required for, neutrophil chemotaxis to fMLP. J Cell Sci. 2008;121:205-14 pubmed publisher
    ..Long-term chemotaxis assays using a pan-PI3K inhibitor, a PI3Kdelta-specific inhibitor or PI3Kgamma-knockout neutrophils, demonstrated no role for PI3K in mediating chemotaxis to fMLP, regardless of the steepness ..
  29. Del Prete A, Vermi W, Dander E, Otero K, Barberis L, Luini W, et al. Defective dendritic cell migration and activation of adaptive immunity in PI3Kgamma-deficient mice. EMBO J. 2004;23:3505-15 pubmed
    Gene-targeted mice were used to evaluate the role of the gamma isoform of phosphoinositide 3-kinase (PI3Kgamma) in dendritic cell (DC) migration and induction of specific T-cell-mediated immune responses...
  30. Schmid M, Avraamides C, Dippold H, Franco I, Foubert P, Ellies L, et al. Receptor tyrosine kinases and TLR/IL1Rs unexpectedly activate myeloid cell PI3k?, a single convergent point promoting tumor inflammation and progression. Cancer Cell. 2011;19:715-27 pubmed publisher
    ..Pharmacological or genetic blockade of p110? suppressed inflammation, growth, and metastasis of implanted and spontaneous tumors, revealing an important therapeutic target in oncology. ..
  31. Hannigan M, Zhan L, Li Z, Ai Y, Wu D, Huang C. Neutrophils lacking phosphoinositide 3-kinase gamma show loss of directionality during N-formyl-Met-Leu-Phe-induced chemotaxis. Proc Natl Acad Sci U S A. 2002;99:3603-8 pubmed
    ..Most of the PI3Kgamma(-/-) neutrophils failed to translocate up the chemotactic gradient...
  32. Barber D, Bartolomé A, Hernandez C, Flores J, Fernandez Arias C, Rodríguez Borlado L, et al. Class IB-phosphatidylinositol 3-kinase (PI3K) deficiency ameliorates IA-PI3K-induced systemic lupus but not T cell invasion. J Immunol. 2006;176:589-93 pubmed
    ..The family is divided into IA isoforms, activated by Tyr kinases and the IB isoform (PI3Kgamma), activated by G protein-coupled receptors...
  33. Nombela Arrieta C, Lacalle R, Montoya M, Kunisaki Y, Megias D, Marqués M, et al. Differential requirements for DOCK2 and phosphoinositide-3-kinase gamma during T and B lymphocyte homing. Immunity. 2004;21:429-41 pubmed
    ..In T cells, this residual migration depended mainly on PI3Kgamma, whereas other PI3K isoforms were implicated in B cells...
  34. Mueller H, Stadtmann A, Van Aken H, Hirsch E, Wang D, Ley K, et al. Tyrosine kinase Btk regulates E-selectin-mediated integrin activation and neutrophil recruitment by controlling phospholipase C (PLC) gamma2 and PI3Kgamma pathways. Blood. 2010;115:3118-27 pubmed publisher
    ..Our data demonstrate the functional importance of this newly identified signaling pathway mediated by E-selectin engagement. ..
  35. Gruen M, Rose C, König C, Gajda M, Wetzker R, Bräuer R. Loss of phosphoinositide 3-kinase gamma decreases migration and activation of phagocytes but not T cell activation in antigen-induced arthritis. BMC Musculoskelet Disord. 2010;11:63 pubmed publisher
    Phosphoinositide 3-kinase gamma (PI3Kgamma) has been depicted as a major regulator of inflammatory processes, including leukocyte activation and migration towards several chemokines...
  36. Randis T, Puri K, Zhou H, Diacovo T. Role of PI3Kdelta and PI3Kgamma in inflammatory arthritis and tissue localization of neutrophils. Eur J Immunol. 2008;38:1215-24 pubmed publisher
    ..Consequently, emphasis has been placed on developing PI3Kgamma selective inhibitors to treat disease states that result from inappropriate tissue accumulation of leukocytes...
  37. Barbi J, Cummings H, Lu B, Oghumu S, Ruckle T, Rommel C, et al. PI3Kgamma (PI3Kgamma) is essential for efficient induction of CXCR3 on activated T cells. Blood. 2008;112:3048-51 pubmed publisher
    The gamma isoform of PI3Kinase (PI3Kgamma) controls leukocyte chemotaxis by participating in GPCR signaling, and by regulating cellular polarization...
  38. Costa C, Barberis L, Ambrogio C, Manazza A, Patrucco E, Azzolino O, et al. Negative feedback regulation of Rac in leukocytes from mice expressing a constitutively active phosphatidylinositol 3-kinase gamma. Proc Natl Acad Sci U S A. 2007;104:14354-9 pubmed
    ..Mice carrying a "knockin" allele of the G protein-coupled receptor (GPCR)-activated PI3Kgamma, encoding a plasma membrane-targeted protein appeared normal, but their leukocytes showed GPCR-uncoupled PIP3 ..
  39. Li H, Park D, Abdul Muneer P, Xu B, Wang H, Xing B, et al. PI3K? inhibition alleviates symptoms and increases axon number in experimental autoimmune encephalomyelitis mice. Neuroscience. 2013;253:89-99 pubmed publisher
    ..Our results indicate that PI3K? contributes to development of autoimmune CNS inflammation and that PI3K? blockade may provide a great potential for treating patients with MS. ..
  40. Weiss Haljiti C, Pasquali C, Ji H, Gillieron C, Chabert C, Curchod M, et al. Involvement of phosphoinositide 3-kinase gamma, Rac, and PAK signaling in chemokine-induced macrophage migration. J Biol Chem. 2004;279:43273-84 pubmed
    ..response depends on Gi activation and largely on the subsequent triggering of phosphoinositide 3-kinase gamma (PI3Kgamma) and Rac...
  41. Roller A, Perino A, Dapavo P, Soro E, Okkenhaug K, Hirsch E, et al. Blockade of phosphatidylinositol 3-kinase PI3K? or PI3K? reduces IL-17 and ameliorates imiquimod-induced psoriasis-like dermatitis. J Immunol. 2012;189:4612-20 pubmed publisher
    ..Taken together, these data indicate that PI3K? and/or PI3K? inhibitors should be considered for treating IL-17-driven diseases, such as psoriasis. ..
  42. Webb L, Vigorito E, Wymann M, Hirsch E, Turner M. Cutting edge: T cell development requires the combined activities of the p110gamma and p110delta catalytic isoforms of phosphatidylinositol 3-kinase. J Immunol. 2005;175:2783-7 pubmed
    ..either die before birth (p110alpha-/- and p110beta-/-) or lack a significant T cell developmental phenotype (p110gamma-/- and p110delta-/-)...
  43. Ji H, Rintelen F, Waltzinger C, Bertschy Meier D, Bilancio A, Pearce W, et al. Inactivation of PI3Kgamma and PI3Kdelta distorts T-cell development and causes multiple organ inflammation. Blood. 2007;110:2940-7 pubmed
    Mice lacking both the p110gamma and p110delta isoforms display severe impairment of thymocyte development...
  44. Lim D, Cho J, Song D, Lee S, Miller M, Broide D. PI3K gamma-deficient mice have reduced levels of allergen-induced eosinophilic inflammation and airway remodeling. Am J Physiol Lung Cell Mol Physiol. 2009;296:L210-9 pubmed publisher
    In this study, we have examined the role of phosphoinositide 3 kinase gamma (PI3Kgamma), a class Ib PI3K, in contributing to airway remodeling utilizing PI3Kgamma-deficient mice exposed to chronic allergen challenge...
  45. Vecchione C, Patrucco E, Marino G, Barberis L, Poulet R, Aretini A, et al. Protection from angiotensin II-mediated vasculotoxic and hypertensive response in mice lacking PI3Kgamma. J Exp Med. 2005;201:1217-28 pubmed
    ..b>PI3Kgamma was found to play a role in angiotensin II-evoked smooth muscle contraction in two crucial, distinct signaling ..
  46. Martin A, Schwartz M, Jameson S, Shimizu Y. Selective regulation of CD8 effector T cell migration by the p110 gamma isoform of phosphatidylinositol 3-kinase. J Immunol. 2008;180:2081-8 pubmed
    Chemokine-mediated T cell migration is essential to an optimal immune response. The p110gamma isoform of PI3K is activated by G protein-coupled receptors and regulates neutrophil and macrophage chemotaxis...
  47. Berod L, Heinemann C, Heink S, Escher A, Stadelmann C, Drube S, et al. PI3K? deficiency delays the onset of experimental autoimmune encephalomyelitis and ameliorates its clinical outcome. Eur J Immunol. 2011;41:833-44 pubmed publisher
    ..These findings demonstrate that PI3K? contributes to the development of autoimmune CNS inflammation. ..
  48. Swat W, Montgrain V, Doggett T, Douangpanya J, Puri K, Vermi W, et al. Essential role of PI3Kdelta and PI3Kgamma in thymocyte survival. Blood. 2006;107:2415-22 pubmed
    ..Surprisingly, genetic deletion of the p110delta and p110gamma catalytic subunits resulted in a dramatic reduction in thymus size, cellularity, and lack of corticomedullary ..
  49. Stadtmann A, Brinkhaus L, Mueller H, Rossaint J, Bolomini Vittori M, Bergmeier W, et al. Rap1a activation by CalDAG-GEFI and p38 MAPK is involved in E-selectin-dependent slow leukocyte rolling. Eur J Immunol. 2011;41:2074-85 pubmed publisher
    ..We found that the small GTPase Rap1 is activated following E-selectin engagement and that blocking Rap1a in Pik3cg-/- mice by a dominant-negative Tat-fusion mutant completely abolished E-selectin-mediated slow rolling...
  50. Boyle K, Gyori D, Sindrilaru A, Scharffetter Kochanek K, Taylor P, Mócsai A, et al. Class IA phosphoinositide 3-kinase β and δ regulate neutrophil oxidase activation in response to Aspergillus fumigatus hyphae. J Immunol. 2011;186:2978-89 pubmed publisher
    ..These results start to define the signaling network controlling neutrophil ROS responses to A. fumigatus hyphae. ..
  51. Ferguson G, Milne L, Kulkarni S, Sasaki T, Walker S, Andrews S, et al. PI(3)Kgamma has an important context-dependent role in neutrophil chemokinesis. Nat Cell Biol. 2007;9:86-91 pubmed
  52. Endo D, Gon Y, Nunomura S, Yamashita K, Hashimoto S, Ra C. PI3Kgamma differentially regulates FcepsilonRI-mediated degranulation and migration of mast cells by and toward antigen. Int Arch Allergy Immunol. 2009;149 Suppl 1:66-72 pubmed publisher
    ..In the present study, we explored the role of PI3Kgamma on mast cell migration...
  53. Kurig B, Shymanets A, Bohnacker T, Prajwal -, Brock C, Ahmadian M, et al. Ras is an indispensable coregulator of the class IB phosphoinositide 3-kinase p87/p110gamma. Proc Natl Acad Sci U S A. 2009;106:20312-7 pubmed publisher
    Class I(B) phosphoinositide 3-kinase gamma (PI3Kgamma) elicits various immunologic and cardiovascular responses; however, the molecular basis for this signal heterogeneity is unclear...
  54. Sasaki T, Irie Sasaki J, Jones R, Oliveira Dos Santos A, Stanford W, Bolon B, et al. Function of PI3Kgamma in thymocyte development, T cell activation, and neutrophil migration. Science. 2000;287:1040-6 pubmed
    ..Viable gene-targeted mice lacking the p110 catalytic subunit of PI3Kgamma were generated...
  55. Russo R, Garcia C, Barcelos L, Rachid M, Guabiraba R, Roffe E, et al. Phosphoinositide 3-kinase ? plays a critical role in bleomycin-induced pulmonary inflammation and fibrosis in mice. J Leukoc Biol. 2011;89:269-82 pubmed publisher
    ..Inhibitors of PI3K? may be beneficial for the treatment of pulmonary fibrosis. ..
  56. Perino A, Ghigo A, Ferrero E, Morello F, Santulli G, Baillie G, et al. Integrating cardiac PIP3 and cAMP signaling through a PKA anchoring function of p110γ. Mol Cell. 2011;42:84-95 pubmed publisher
    ..Pharmacological inhibition of p110γ normalizes β-adrenergic receptor density and improves contractility in failing hearts. ..
  57. Chang J, Sukhova G, Libby P, Schvartz E, Lichtenstein A, Field S, et al. Deletion of the phosphoinositide 3-kinase p110gamma gene attenuates murine atherosclerosis. Proc Natl Acad Sci U S A. 2007;104:8077-82 pubmed
    ..This activation is markedly reduced or absent in macrophages lacking p110gamma, the catalytic subunit of class Ib PI3-kinase...
  58. Condliffe A, Davidson K, Anderson K, Ellson C, Crabbe T, Okkenhaug K, et al. Sequential activation of class IB and class IA PI3K is important for the primed respiratory burst of human but not murine neutrophils. Blood. 2005;106:1432-40 pubmed
    ..fMLP) results in biphasic activation of PI3K; the first phase is largely dependent on PI3Kgamma, and the second phase is largely dependent on PI3Kdelta...
  59. Li L, MacDonald P, Ahn D, Oudit G, Backx P, Brubaker P. Role of phosphatidylinositol 3-kinasegamma in the beta-cell: interactions with glucagon-like peptide-1. Endocrinology. 2006;147:3318-25 pubmed
    ..These studies reveal a new role for PI3-Kgamma as a positive regulator of insulin secretion, and reinforce the importance of GLP-1 for the maintenance of normal beta-cell function. ..
  60. Suire S, Coadwell J, Ferguson G, Davidson K, Hawkins P, Stephens L. p84, a new Gbetagamma-activated regulatory subunit of the type IB phosphoinositide 3-kinase p110gamma. Curr Biol. 2005;15:566-70 pubmed
    A variety of genetic and inhibitor studies have shown that phosphoinositide 3-kinase gamma (PI3Kgamma) plays an essential role in a number of physiological responses, including neutrophil chemotaxis, mast cell degranulation, and cardiac ..
  61. Patrucco E, Notte A, Barberis L, Selvetella G, Maffei A, Brancaccio M, et al. PI3Kgamma modulates the cardiac response to chronic pressure overload by distinct kinase-dependent and -independent effects. Cell. 2004;118:375-87 pubmed
    The G protein-coupled, receptor-activated phosphoinositide 3-kinase gamma (PI3Kgamma) mediates inflammatory responses and negatively controls cardiac contractility by reducing cAMP concentration...
  62. Suire S, Condliffe A, Ferguson G, Ellson C, Guillou H, Davidson K, et al. Gbetagammas and the Ras binding domain of p110gamma are both important regulators of PI(3)Kgamma signalling in neutrophils. Nat Cell Biol. 2006;8:1303-9 pubmed
    ..We conclude that Gbetagammas, p101 and the Ras-RBD interaction all have important roles in the regulation of PI(3)Kgamma in vivo and that they can simultaneously, but differentially, control distinct PI(3)Kgamma effectors. ..
  63. Thomas M, Edwards M, Sawicka E, Duggan N, Hirsch E, Wymann M, et al. Essential role of phosphoinositide 3-kinase gamma in eosinophil chemotaxis within acute pulmonary inflammation. Immunology. 2009;126:413-22 pubmed publisher
    We and others have established an important role for phosphoinositide-3 kinase gamma (PI3Kgamma) in the chemotactic responses of macrophages and neutrophils...
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    Phosphoinositide 3-kinases (PI3Ks) have been considered important in leukocyte motility. PI3Kgamma, the class I(B) PI3K, expressed prominently in leukocytes and also in endothelial cells, mediates leukocyte functional responses induced ..
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    ..PI3K? is a promising target for the treatment of aortic fibroproliferative pathologies. ..