Gene Symbol: Pik3r1
Description: phosphoinositide-3-kinase regulatory subunit 1
Alias: PI3KA, phosphatidylinositol 3-kinase regulatory subunit alpha, PI3-kinase p85 subunit alpha, PI3-kinase regulatory subunit alpha, PI3-kinase subunit p85-alpha, PI3K regulatory subunit alpha, Phosphoinositide 3-kinase p85 (other splicing variants: p55 and p50), Phosphoinositide 3-kinase, regulatory subunit, polypeptide 1 (p85 alpha), phosphatidylinositol 3-kinase 85 kDa regulatory subunit alpha, phosphatidylinositol 3-kinase p85 alpha, phosphatidylinositol 3-kinase, regulatory subunit, polypeptide 1 (p85 alpha), phosphoinositide-3-kinase, regulatory subunit 1 (alpha), ptdIns-3-kinase p85-alpha, ptdIns-3-kinase regulatory subunit alpha, ptdIns-3-kinase regulatory subunit p85-alpha
Species: rat
Products:     Pik3r1

Top Publications

  1. Byun J, Kim M, Yoon C, Cha H, Yoon G, Lee S. Oncogenic Ras signals through activation of both phosphoinositide 3-kinase and Rac1 to induce c-Jun NH2-terminal kinase-mediated, caspase-independent cell death. Mol Cancer Res. 2009;7:1534-42 pubmed publisher
  2. Luo J, Field S, Lee J, Engelman J, Cantley L. The p85 regulatory subunit of phosphoinositide 3-kinase down-regulates IRS-1 signaling via the formation of a sequestration complex. J Cell Biol. 2005;170:455-64 pubmed
    ..These results suggest a mechanism of signal down-regulation of IRS-1 that is mediated by monomeric p85 through the formation of a sequestration complex between p85 and IRS-1. ..
  3. Engelman J, Luo J, Cantley L. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet. 2006;7:606-19 pubmed
    ..In light of the recent advances in our understanding of the function of PI3Ks in the pathogenesis of diabetes and cancer, we discuss the exciting therapeutic opportunities for targeting this pathway to treat these diseases. ..
  4. Terauchi Y, Tsuji Y, Satoh S, Minoura H, Murakami K, Okuno A, et al. Increased insulin sensitivity and hypoglycaemia in mice lacking the p85 alpha subunit of phosphoinositide 3-kinase. Nat Genet. 1999;21:230-5 pubmed
    ..we generated mice with a targeted disruption of the gene encoding the p85alpha regulatory subunit of PI3K (Pik3r1; refs 3-5)...
  5. Inukai K, Funaki M, Ogihara T, Katagiri H, Kanda A, Anai M, et al. p85alpha gene generates three isoforms of regulatory subunit for phosphatidylinositol 3-kinase (PI 3-Kinase), p50alpha, p55alpha, and p85alpha, with different PI 3-kinase activity elevating responses to insulin. J Biol Chem. 1997;272:7873-82 pubmed
    ..Each of the three alpha isoforms has a different function and may have specific roles in various tissues. ..
  6. Esteve P, Robledo O, Potworowski E, St Pierre Y. Induced expression of MMP-9 in C6 glioma cells is inhibited by PDGF via a PI 3-kinase-dependent pathway. Biochem Biophys Res Commun. 2002;296:864-9 pubmed
    ..Taken together, these results suggest that PI 3-kinase may act as a negative regulator of MMP-9 expression in C6 glioma cells. ..
  7. Liu L, Zhao X, Pierre S, Askari A. Association of PI3K-Akt signaling pathway with digitalis-induced hypertrophy of cardiac myocytes. Am J Physiol Cell Physiol. 2007;293:C1489-97 pubmed
  8. Del Re D, Miyamoto S, Brown J. Focal adhesion kinase as a RhoA-activable signaling scaffold mediating Akt activation and cardiomyocyte protection. J Biol Chem. 2008;283:35622-9 pubmed publisher
    ..We suggest that RhoA-mediated effects on the cardiomyocyte cytoskeleton provide a novel mechanism for protection from apoptosis...
  9. Laprise P, Viel A, Rivard N. Human homolog of disc-large is required for adherens junction assembly and differentiation of human intestinal epithelial cells. J Biol Chem. 2004;279:10157-66 pubmed
    ..We conclude that hDlg may be a determinant in E-cadherin-mediated adhesion and signaling in mammalian epithelial cells. ..

More Information


  1. Park S, Zhou Y, Lee J, Lu A, Sun C, Chung J, et al. The regulatory subunits of PI3K, p85alpha and p85beta, interact with XBP-1 and increase its nuclear translocation. Nat Med. 2010;16:429-37 pubmed publisher
    ..Here, we show that the regulatory subunits of phosphotidyl inositol 3-kinase (PI3K), p85alpha (encoded by Pik3r1) and p85beta (encoded by Pik3r2) form heterodimers that are disrupted by insulin treatment...
  2. Soltoff S, Cantley L. p120cbl is a cytosolic adapter protein that associates with phosphoinositide 3-kinase in response to epidermal growth factor in PC12 and other cells. J Biol Chem. 1996;271:563-7 pubmed
    ..p120cbl was also present in A431 cells and offers an additional pathway by which EGF can activate PI 3-kinase in these cells. ..
  3. Antonetti D, Algenstaedt P, Kahn C. Insulin receptor substrate 1 binds two novel splice variants of the regulatory subunit of phosphatidylinositol 3-kinase in muscle and brain. Mol Cell Biol. 1996;16:2195-203 pubmed
  4. Yang F, Chen S, Robling A, Yu X, Nebesio T, Yan J, et al. Hyperactivation of p21ras and PI3K cooperate to alter murine and human neurofibromatosis type 1-haploinsufficient osteoclast functions. J Clin Invest. 2006;116:2880-91 pubmed
    ..Collectively, our results identify a what we believe to be a novel cellular and biochemical NF1-haploinsufficient phenotype in osteoclasts that has potential implications for the pathogenesis of NF1 bone disease. ..
  5. Bock H, Jossin Y, Liu P, Forster E, May P, Goffinet A, et al. Phosphatidylinositol 3-kinase interacts with the adaptor protein Dab1 in response to Reelin signaling and is required for normal cortical lamination. J Biol Chem. 2003;278:38772-9 pubmed
    ..Using a neuronal migration assay, we also show that PI3K signaling is required for the formation of a normal cortical plate, a step that is dependent upon Reelin signaling. ..
  6. Biswas S, Zhao Y, Nagalingam A, Gardner T, Sandirasegarane L. PDGF- and insulin/IGF-1-specific distinct modes of class IA PI 3-kinase activation in normal rat retinas and RGC-5 retinal ganglion cells. Invest Ophthalmol Vis Sci. 2008;49:3687-98 pubmed publisher
    ..PDGF-induced PI 3-kinase/PIP3/Akt axis may provide new therapeutic approaches to ameliorate cell death in diabetic retinopathy and other retinal neurodegenerations. ..
  7. Uranga R, Mateos M, Giusto N, Salvador G. Activation of phosphoinositide-3 kinase/Akt pathway by FeSO4 in rat cerebral cortex synaptic endings. J Neurosci Res. 2007;85:2924-32 pubmed
    ..Our results demonstrate that free iron provokes the early activation of PI3K/Akt pathway, but this activation is not sufficient for protecting synaptic endings from oxidative damage. ..
  8. Elsawa S, Taylor W, Petty C, Marriott I, Weinstock J, Bost K. Reduced CTL response and increased viral burden in substance P receptor-deficient mice infected with murine gamma-herpesvirus 68. J Immunol. 2003;170:2605-12 pubmed
    ..These studies demonstrate that genetic elimination of substance P receptors in mice results in an increased gamma-herpesvirus burden and an altered host response. ..
  9. Scioscia M, Gumaa K, Kunjara S, Paine M, Selvaggi L, Rodeck C, et al. Insulin resistance in human preeclamptic placenta is mediated by serine phosphorylation of insulin receptor substrate-1 and -2. J Clin Endocrinol Metab. 2006;91:709-17 pubmed
    ..These results seem to confirm an insulin-resistant state in PE placenta and shed a different light on its role in the pathogenesis of this disease with potential therapeutic implications. ..
  10. Hiatt K, Ingram D, Huddleston H, Spandau D, Kapur R, Clapp D. Loss of the nf1 tumor suppressor gene decreases fas antigen expression in myeloid cells. Am J Pathol. 2004;164:1471-9 pubmed
    ..Thus, therapies designed to decrease p21(ras) activity and up-regulate Fas antigen expression may limit the pathological accumulation of myeloid cells in disease states where p21(ras) is hyperactivated. ..
  11. Lee F, Xue S, Pei L, Vukusic B, Chery N, Wang Y, et al. Dual regulation of NMDA receptor functions by direct protein-protein interactions with the dopamine D1 receptor. Cell. 2002;111:219-30 pubmed
    ..While one interaction is involved in the inhibition of NMDA receptor-gated currents, the other is implicated in the attenuation of NMDA receptor-mediated excitotoxicity through a PI-3 kinase-dependent pathway. ..
  12. Kaliman P, Canicio J, Shepherd P, Beeton C, Testar X, Palacin M, et al. Insulin-like growth factors require phosphatidylinositol 3-kinase to signal myogenesis: dominant negative p85 expression blocks differentiation of L6E9 muscle cells. Mol Endocrinol. 1998;12:66-77 pubmed
    ..In all, data presented here indicate that PI 3-kinase is essential for IGF-induced muscle differentiation and that the specific PI 3-kinase subclass involved in myogenesis is the heterodimeric p85-p110 enzyme. ..
  13. Chae H, Kim H, Bae J, Chae S, Ha K, Chae S. Signal transduction of the protective effect of insulin like growth factor-1 on adriamycin-induced apoptosis in cardiac muscle cells. Arch Pharm Res. 2004;27:324-33 pubmed
    ..Although IGF-I activates several signaling pathways that contribute to its protective effect in other cell types, only activation of PI 3-kinase contributes to this effect in H9C2 cardiac muscle cells. ..
  14. Yu D, Peng X, Zhao L, Tian L. [Effects of alcohol and high-fat diet on the expression of phosphatidylinositol 3-kinase in rat adipose tissue]. Wei Sheng Yan Jiu. 2009;38:395-7 pubmed
    ..The changes of PI-3K-P85alpha expression in adipose tissue may be one of the molecular mechanism of insulin resistance induced by alcohol combined high-fat diet. ..
  15. Sedding D, Hermsen J, Seay U, Eickelberg O, Kummer W, Schwencke C, et al. Caveolin-1 facilitates mechanosensitive protein kinase B (Akt) signaling in vitro and in vivo. Circ Res. 2005;96:635-42 pubmed
    ..Our study provides evidence that PI3-K/Akt is critically involved in mechanotransduction of VSMC in vitro and within the vasculature in vivo. Furthermore, caveolin-1 is essential for the integrin-mediated activation of PI3-K/Akt. ..
  16. Nedachi T, Akahori M, Ariga M, Sakamoto H, Suzuki N, Umesaki K, et al. Tyrosine kinase and phosphatidylinositol 3-kinase activation are required for cyclic adenosine 3',5'-monophosphate-dependent potentiation of deoxyribonucleic acid synthesis induced by insulin-like growth factor-I in FRTL-5 cells. Endocrinology. 2000;141:2429-38 pubmed
    ..These mechanisms appear to be necessary for cAMP-dependent potentiation of the DNA synthesis induced by IGF-I. ..
  17. Egawa K, Maegawa H, Shimizu S, Morino K, Nishio Y, Bryer Ash M, et al. Protein-tyrosine phosphatase-1B negatively regulates insulin signaling in l6 myocytes and Fao hepatoma cells. J Biol Chem. 2001;276:10207-11 pubmed
    ..The present findings demonstrate that PTP1B negatively regulates insulin signaling in L6 and Fao cells, suggesting that PTP1B plays an important role in insulin resistance in muscle and liver. ..
  18. Tappia P, Guzman C, Dunn L, Aroutiounova N. Adverse cardiac remodeling due to maternal low protein diet is associated with alterations in expression of genes regulating glucose metabolism. Nutr Metab Cardiovasc Dis. 2013;23:130-5 pubmed publisher
  19. Kwon H, Lee J, Jeong K, Jang D, Pak Y. Fatty acylated caveolin-2 is a substrate of insulin receptor tyrosine kinase for insulin receptor substrate-1-directed signaling activation. Biochim Biophys Acta. 2015;1853:1022-34 pubmed publisher
    ..In conclusion, fatty acylated cav-2 is a new substrate of IR tyrosine kinase, and the fatty acylation and phosphorylation of cav-2 present novel mechanisms by which insulin signaling is activated. ..
  20. Gustafson T, He W, Craparo A, Schaub C, O Neill T. Phosphotyrosine-dependent interaction of SHC and insulin receptor substrate 1 with the NPEY motif of the insulin receptor via a novel non-SH2 domain. Mol Cell Biol. 1995;15:2500-8 pubmed
    ..The SAIN domain appears to represent a novel motif which is able to interact with autophosphorylated receptors such as the IR. ..
  21. Gao B, Hansen H, Chen H, Feener E. Angiotensin II stimulates phosphorylation of an ectodomain-truncated platelet-derived growth factor receptor-beta and its binding to class IA PI3K in vascular smooth muscle cells. Biochem J. 2006;397:337-44 pubmed
    ..Our result suggests that the p70 PDGFR-beta functions as an adapter that recruits PI3K to the membrane upon AT1 receptor stimulation. ..
  22. Francis S, Sunshine C, Kirk K. Coordinate regulation of catecholamine uptake by rab3 and phosphoinositide 3-kinase. J Biol Chem. 2002;277:7816-23 pubmed
    ..Our results indicate that rab3 and PI3K positively and coordinately regulate NE uptake in PC12 neuroendocrine cells at least in part by stimulating the secretory vesicle uptake step. ..
  23. Haba M, Hatakeyama N, Kinoshita H, Teramae H, Azma T, Hatano Y, et al. The modulation of vascular ATP-sensitive K+ channel function via the phosphatidylinositol 3-kinase-Akt pathway activated by phenylephrine. J Pharmacol Exp Ther. 2010;334:673-8 pubmed publisher
    ..Therefore, activation of the PI3K-Akt pathway seems to play a role in the impairment of ATP-sensitive K(+) channel function in vascular smooth muscle exposed to alpha-1 adrenergic stimuli. ..
  24. Taniguchi C, Aleman J, Ueki K, Luo J, Asano T, Kaneto H, et al. The p85alpha regulatory subunit of phosphoinositide 3-kinase potentiates c-Jun N-terminal kinase-mediated insulin resistance. Mol Cell Biol. 2007;27:2830-40 pubmed
    ..Thus, p85alpha plays a dual role in regulating insulin sensitivity and may mediate cross talk between the PI3K and stress kinase pathways. ..
  25. Kawashima A, Harada T, Kami H, Yano T, Imada K, Mizuguchi K. Effects of eicosapentaenoic acid on synaptic plasticity, fatty acid profile and phosphoinositide 3-kinase signaling in rat hippocampus and differentiated PC12 cells. J Nutr Biochem. 2010;21:268-77 pubmed publisher
  26. Shimizu S, Maegawa H, Egawa K, Shi K, Bryer Ash M, Kashiwagi A. Mechanism for differential effect of protein-tyrosine phosphatase 1B on Akt versus mitogen-activated protein kinase in 3T3-L1 adipocytes. Endocrinology. 2002;143:4563-9 pubmed
    ..These data demonstrate that PTP1B negatively regulates insulin signaling in the MAPK cascade to a much greater extent than the Akt pathway in some cell lines, especially in L1 adipocytes. ..
  27. Vetiska S, Ahmadian G, Ju W, Liu L, Wymann M, Wang Y. GABAA receptor-associated phosphoinositide 3-kinase is required for insulin-induced recruitment of postsynaptic GABAA receptors. Neuropharmacology. 2007;52:146-55 pubmed
    ..Our results imply a mechanism whereby insulin can regulate changes in synaptic transmission through its downstream actions on the GABAA receptor. ..
  28. Hirsch E, Costa C, Ciraolo E. Phosphoinositide 3-kinases as a common platform for multi-hormone signaling. J Endocrinol. 2007;194:243-56 pubmed
    ..This review will thus focus on the different pathways that converge on PI3K activation, with particular attention to the paradigmatic PI3K involvement in insulin signaling. ..
  29. Argetsinger L, Hsu G, Myers M, Billestrup N, White M, Carter Su C. Growth hormone, interferon-gamma, and leukemia inhibitory factor promoted tyrosyl phosphorylation of insulin receptor substrate-1. J Biol Chem. 1995;270:14685-92 pubmed
  30. Franch H, Raissi S, Wang X, Zheng B, Bailey J, Price S. Acidosis impairs insulin receptor substrate-1-associated phosphoinositide 3-kinase signaling in muscle cells: consequences on proteolysis. Am J Physiol Renal Physiol. 2004;287:F700-6 pubmed
    ..We conclude that acidosis accelerates protein degradation by impairing insulin signaling through PI3K in muscle cells. ..
  31. Zhou C, Li C, Li D, Wang Y, Shao W, You Y, et al. BIG1, a brefeldin A-inhibited guanine nucleotide-exchange protein regulates neurite development via PI3K-AKT and ERK signaling pathways. Neuroscience. 2013;254:361-8 pubmed publisher
    ..The newly recognized function integrates the function of BIG1 in membrane trafficking with the activation of PI3K-AKT and ERK signaling pathways which are critical in neurite development. ..
  32. Zhang H, Li J, Li R, Zhang Q, Ma H, Ji Q, et al. Reduced cardiotropic response to insulin in spontaneously hypertensive rats: role of peroxisome proliferator-activated receptor-gamma-initiated signaling. J Hypertens. 2008;26:560-9 pubmed publisher
  33. Cazzolli R, Mitchell T, Burchfield J, Pedersen D, Turner N, Biden T, et al. Dilinoleoyl-phosphatidic acid mediates reduced IRS-1 tyrosine phosphorylation in rat skeletal muscle cells and mouse muscle. Diabetologia. 2007;50:1732-42 pubmed
    ..These data indicate that linoleate-derived phosphatidic acid is a novel lipid species that contributes independently of protein kinase C to IRS-1 signalling defects in muscle cells in response to lipid oversupply. ..
  34. Liu I, Tzeng T, Liou S, Lan T. Myricetin, a naturally occurring flavonol, ameliorates insulin resistance induced by a high-fructose diet in rats. Life Sci. 2007;81:1479-88 pubmed
    ..These findings indicate that myricetin improves insulin sensitivity through the enhancement of insulin action on IRS-1-associated PI 3-kinase and GLUT 4 activity in soleus muscles of animals exhibiting insulin resistance. ..
  35. Slomiany B, Slomiany A. Role of ghrelin-induced phosphatidylinositol 3-kinase activation in modulation of gastric mucosal inflammatory responses to Helicobacter pylori. Inflammopharmacology. 2014;22:169-77 pubmed publisher
    ..pylori LPS relies on PI3K activation that depends on PLC/PKC signaling pathway, and that PI3K activity is required for the induction of cSrc/Akt activation. ..
  36. Gentile A, Trusolino L, Comoglio P. The Met tyrosine kinase receptor in development and cancer. Cancer Metastasis Rev. 2008;27:85-94 pubmed publisher
    ..Several approaches have been recently developed to interfere with the tumorigenic and metastatic processes triggered by Met. ..
  37. Kim Y, Nakajima R, Matsuo T, Inoue T, Sekine T, Komuro M, et al. Gene expression of insulin signal-transduction pathway intermediates is lower in rats fed a beef tallow diet than in rats fed a safflower oil diet. Metabolism. 1996;45:1080-8 pubmed
    ..We conclude that long-term feeding of a high-fat diet with saturated fatty acids induces decrease in IRS-1 and PI 3-kinase mRNA and protein levels, causing insulin resistance in skeletal muscle. ..
  38. Patti M, Virkamaki A, Landaker E, Kahn C, Yki Jarvinen H. Activation of the hexosamine pathway by glucosamine in vivo induces insulin resistance of early postreceptor insulin signaling events in skeletal muscle. Diabetes. 1999;48:1562-71 pubmed
  39. Pezet S, Marchand F, D Mello R, Grist J, Clark A, Malcangio M, et al. Phosphatidylinositol 3-kinase is a key mediator of central sensitization in painful inflammatory conditions. J Neurosci. 2008;28:4261-70 pubmed publisher
    ..Our study suggests that PI3K is a major factor in the expression of central sensitization after noxious inflammatory stimuli. ..
  40. Qiu S, Zhao L, Korwek K, Weeber E. Differential reelin-induced enhancement of NMDA and AMPA receptor activity in the adult hippocampus. J Neurosci. 2006;26:12943-55 pubmed
    ..Together, these results reveal a differential functional coupling of reelin signaling with NMDAR and AMPAR function and define a novel mechanism for controlling synaptic strength and plasticity in the adult hippocampus. ..
  41. Fukao T, Yamada T, Tanabe M, Terauchi Y, Ota T, Takayama T, et al. Selective loss of gastrointestinal mast cells and impaired immunity in PI3K-deficient mice. Nat Immunol. 2002;3:295-304 pubmed
    ..This finding highlights the importance of the TH2 response in the control of nematode infection. Thus, PI3K likely plays an essential role in host immune responses by regulating both the development and induction of mast cells. ..
  42. Winnay J, Boucher J, Mori M, Ueki K, Kahn C. A regulatory subunit of phosphoinositide 3-kinase increases the nuclear accumulation of X-box-binding protein-1 to modulate the unfolded protein response. Nat Med. 2010;16:438-45 pubmed publisher
    ..Mice with deletion of p85alpha in liver (L-Pik3r1(-/-)) show a similar attenuated UPR after tunicamycin administration, leading to an increased inflammatory ..
  43. Tung W, Lee I, Hsieh H, Yang C. EV71 induces COX-2 expression via c-Src/PDGFR/PI3K/Akt/p42/p44 MAPK/AP-1 and NF-kappaB in rat brain astrocytes. J Cell Physiol. 2010;224:376-86 pubmed publisher
    ..These results demonstrate that in RBA-1 cells, EV71-induced COX-2 expression associated with PGE(2) production is mediated through activation of c-Src/PDGFR/PI3K/Akt/p42/p44 MAPK to initiate the expression of AP-1. ..
  44. Torella D, Gasparri C, Ellison G, Curcio A, Leone A, Vicinanza C, et al. Differential regulation of vascular smooth muscle and endothelial cell proliferation in vitro and in vivo by cAMP/PKA-activated p85alphaPI3K. Am J Physiol Heart Circ Physiol. 2009;297:H2015-25 pubmed publisher
    ..By reducing neointimal hyperplasia without inhibiting endothelial regeneration, it exerts a protective effect against restenosis after balloon injury. ..
  45. Zubcevic J, Waki H, Diez Freire C, Gampel A, Raizada M, Paton J. Chronic blockade of phosphatidylinositol 3-kinase in the nucleus tractus solitarii is prohypertensive in the spontaneously hypertensive rat. Hypertension. 2009;53:97-103 pubmed publisher
    ..7+/-0.07 to 0.5+/-0.04 ms/mm Hg; P<0.001) in the SHRs. Thus, PI3K signaling in the nucleus tractus solitarii of SHR restrains arterial pressure in this animal model of neurogenic hypertension. ..
  46. Lin Y, Yang Z, Xu A, Dong P, Huang Y, Liu H, et al. PIK3R1 negatively regulates the epithelial-mesenchymal transition and stem-like phenotype of renal cancer cells through the AKT/GSK3β/CTNNB1 signaling pathway. Sci Rep. 2015;5:8997 pubmed publisher
    ..We have reported a nonsense mutation in PIK3R1, which encodes the regulatory subunit of PI3K, in a metastatic RCC (mRCC), while the mutation was absent in the ..
  47. Watson M, Coghlan M, Hundal H. Modulating serine palmitoyl transferase (SPT) expression and activity unveils a crucial role in lipid-induced insulin resistance in rat skeletal muscle cells. Biochem J. 2009;417:791-801 pubmed publisher
  48. Anggono V, Robinson P. Syndapin I and endophilin I bind overlapping proline-rich regions of dynamin I: role in synaptic vesicle endocytosis. J Neurochem. 2007;102:931-43 pubmed
    ..We propose syndapin and endophilin function either at different stages during SVE or in mechanistically distinct types of SVE. ..
  49. Milarski K, Lazar D, Wiese R, Saltiel A. Detection of a 60 kDa tyrosine-phosphorylated protein in insulin-stimulated hepatoma cells that associates with the SH2 domain of phosphatidylinositol 3-kinase. Biochem J. 1995;308 ( Pt 2):579-83 pubmed
    ..The presence of this 60 kDa tyrosine-phosphorylated protein in adipocytes and hepatoma cells suggests that it represents another important intermediate in the insulin-receptor signal-transduction pathway. ..
  50. Liolitsa D, Powell J, Lovestone S. Genetic variability in the insulin signalling pathway may contribute to the risk of late onset Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2002;73:261-6 pubmed
    ..The p85alpha subunit of phosphatidyl inositol 3 kinase (PIK3R1) and the regulatory subunit 3 of protein phosphatase 1 (PPP1R3) were selected as candidate genes because both ..
  51. Song L, Li J, Ye J, Yu G, Ding J, Zhang D, et al. p85alpha acts as a novel signal transducer for mediation of cellular apoptotic response to UV radiation. Mol Cell Biol. 2007;27:2713-31 pubmed
  52. Cavet M, Smolock E, Ozturk O, World C, Pang J, Konishi A, et al. Gas6-axl receptor signaling is regulated by glucose in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2008;28:886-91 pubmed publisher
    ..This study demonstrates a role for glucose in altering Axl signaling through coupling to binding partners and suggests a mechanism by which Axl contributes to VSMC dysfunction in diabetes. ..
  53. Yamaguchi Y, Flier J, Benecke H, Ransil B, Moller D. Ligand-binding properties of the two isoforms of the human insulin receptor. Endocrinology. 1993;132:1132-8 pubmed
    ..These findings further support the idea that the 2 isoforms of the insulin receptor are functionally distinct in important ways. ..
  54. Choi W, Sung C. Characterization of insulin receptor substrate 3 in rat liver derived cells. Biochem Biophys Res Commun. 2000;272:953-8 pubmed
    ..Unlike related IRS-1/2 that is transiently phosphorylated, IRS-3 shows robust and prolonged tyrosine phosphorylation upon insulin treatment of cells and may play a role in delayed and/or prolonged insulin actions. ..
  55. Kong M, Mounier C, Wu J, Posner B. Epidermal growth factor-induced phosphatidylinositol 3-kinase activation and DNA synthesis. Identification of Grb2-associated binder 2 as the major mediator in rat hepatocytes. J Biol Chem. 2000;275:36035-42 pubmed
    ..We also found that the PI3-kinase activity associated with Gab2 was totally abolished by dominant negative p85. Thus, Gab2 appears to be the principal EGF-induced PY protein recruiting and activating PI3-kinase and mitogenesis. ..
  56. Andrade M, Hiragun T, Beaven M. Dexamethasone suppresses antigen-induced activation of phosphatidylinositol 3-kinase and downstream responses in mast cells. J Immunol. 2004;172:7254-62 pubmed
  57. Toriyama M, Shimada T, Kim K, Mitsuba M, Nomura E, Katsuta K, et al. Shootin1: A protein involved in the organization of an asymmetric signal for neuronal polarization. J Cell Biol. 2006;175:147-57 pubmed
    ..We propose that shootin1 is involved in the generation of internal asymmetric signals required for neuronal polarization. ..
  58. Kaplan Albuquerque N, Garat C, Desseva C, Jones P, Nemenoff R. Platelet-derived growth factor-BB-mediated activation of Akt suppresses smooth muscle-specific gene expression through inhibition of mitogen-activated protein kinase and redistribution of serum response factor. J Biol Chem. 2003;278:39830-8 pubmed
    ..This was associated with appearance of serum response factor in the cytoplasm. These data indicate that activation of p85/p110 alpha/Akt mediates suppression of SM gene expression by PDGF. ..
  59. Riggins R, DeBerry R, Toosarvandani M, Bouton A. Src-dependent association of Cas and p85 phosphatidylinositol 3'-kinase in v-crk-transformed cells. Mol Cancer Res. 2003;1:428-37 pubmed
    ..This suggests that the association of Cas with p85 PI3K may play a role in uncoupling growth regulatory pathways through v-Crk. ..
  60. Kawanaka H, Jones M, Szabo I, Baatar D, Pai R, Tsugawa K, et al. Activation of eNOS in rat portal hypertensive gastric mucosa is mediated by TNF-alpha via the PI 3-kinase-Akt signaling pathway. Hepatology. 2002;35:393-402 pubmed
    ..In conclusion, these findings show that in PHT gastric mucosa, TNF-alpha stimulates eNOS phosphorylation at serine 1177 (required for its activation) via the PI 3-kinase-Akt signal transduction pathway. ..
  61. Tsuda M, Toyomitsu E, Kometani M, Tozaki Saitoh H, Inoue K. Mechanisms underlying fibronectin-induced up-regulation of P2X4R expression in microglia: distinct roles of PI3K-Akt and MEK-ERK signalling pathways. J Cell Mol Med. 2009;13:3251-9 pubmed publisher
    ..Together, these results suggest that the PI3K-Akt and MEK-ERK signalling cascades have distinct roles in the up-regulation of P2X(4)R expression in microglia at transcriptional and post-transcriptional levels, respectively. ..
  62. de Castro Barbosa T, de Carvalho J, Poyares L, Bordin S, Machado U, Nunes M. Potential role of growth hormone in impairment of insulin signaling in skeletal muscle, adipose tissue, and liver of rats chronically treated with arginine. Endocrinology. 2009;150:2080-6 pubmed publisher
  63. Majumdar A, Du J. Phosphatidylinositol 3-kinase/Akt signaling stimulates colonic mucosal cell survival during aging. Am J Physiol Gastrointest Liver Physiol. 2006;290:G49-55 pubmed
    ..We conclude that the constitutive activation of the PI3K/Akt-signaling pathway is partly responsible for the age-related increase in colonic mucosal cell survival. This is evident throughout the entire length of the colonic crypt. ..
  64. Rottapel R, Turck C, Casteran N, Liu X, Birnbaum D, Pawson T, et al. Substrate specificities and identification of a putative binding site for PI3K in the carboxy tail of the murine Flt3 receptor tyrosine kinase. Oncogene. 1994;9:1755-65 pubmed
    ..FF3 associates with PI3K activity and the SH2 domains of p85 and Grb-2. Phosphopeptide competition experiments suggest that the PI3K binding site is located outside of the kinase insert in the carboxy tail of the receptor. ..
  65. Craparo A, O Neill T, Gustafson T. Non-SH2 domains within insulin receptor substrate-1 and SHC mediate their phosphotyrosine-dependent interaction with the NPEY motif of the insulin-like growth factor I receptor. J Biol Chem. 1995;270:15639-43 pubmed
    ..We conclude that the interactions of SHC and IRS-1 with the IGFIR are similar to those which we have previously defined with the insulin receptor. ..
  66. He L, Marecki J, Serrero G, Simmen F, Ronis M, Badger T. Dose-dependent effects of alcohol on insulin signaling: partial explanation for biphasic alcohol impact on human health. Mol Endocrinol. 2007;21:2541-50 pubmed
  67. Li Q, Li G, Lan X, Zheng M, Chen K, Cao C, et al. Receptor interacting protein 3 suppresses vascular smooth muscle cell growth by inhibition of the phosphoinositide 3-kinase-Akt axis. J Biol Chem. 2010;285:9535-44 pubmed publisher
    ..These findings reveal a novel growth-suppressive action of RIP3, marking RIP3 as an important factor to prevent excessive mitogenic stimulation- or injury-induced vascular smooth muscle cells hyperplasia. ..
  68. Wu Y, Zhao W, Zhao J, Zhang Y, Qin W, Pan J, et al. REDD1 is a major target of testosterone action in preventing dexamethasone-induced muscle loss. Endocrinology. 2010;151:1050-9 pubmed publisher
    ..These data suggest that testosterone blocks dexamethasone-induced changes in expression of REDD1 and other genes that collectively would otherwise down-regulate mTOR activity and hence also down-regulate protein synthesis. ..
  69. Feres N, Reis S, Veloso R, Arantes V, Souza L, Carneiro E, et al. Soybean diet alters the insulin-signaling pathway in the liver of rats recovering from early-life malnutrition. Nutrition. 2010;26:441-8 pubmed publisher
    ..Adult rats maintained with a soybean diet exhibited insulin resistance due, at least in part, to alterations in the early steps of the insulin signal transduction pathway. ..
  70. Page K, Malik R, Ripple J, Anday E. Maternal and postweaning diet interaction alters hypothalamic gene expression and modulates response to a high-fat diet in male offspring. Am J Physiol Regul Integr Comp Physiol. 2009;297:R1049-57 pubmed publisher
  71. Mannella P, Brinton R. Estrogen receptor protein interaction with phosphatidylinositol 3-kinase leads to activation of phosphorylated Akt and extracellular signal-regulated kinase 1/2 in the same population of cortical neurons: a unified mechanism of estrogen action. J Neurosci. 2006;26:9439-47 pubmed
    ..Implications of these results for understanding estrogen mechanism of action in neurons and therapeutic development are considered. ..
  72. Pelletier A, Tardif A, Gingras M, Chiasson J, Coderre L. Chronic exposure to ketone bodies impairs glucose uptake in adult cardiomyocytes in response to insulin but not vanadate: the role of PI3-K. Mol Cell Biochem. 2007;296:97-108 pubmed
    ..Furthermore, vanadate can bypass insulin resistance and stimulate glucose uptake in OHB-treated cardiomyocytes. ..
  73. Hellwinkel O, Rogmann J, Asong L, Luebke A, Eichelberg C, Ahyai S, et al. A comprehensive analysis of transcript signatures of the phosphatidylinositol-3 kinase/protein kinase B signal-transduction pathway in prostate cancer. BJU Int. 2008;101:1454-60 pubmed publisher
    ..These changes were in effectors of the pathway, especially PIK3 p85 alpha (PIK3R1) and integrin-linked kinase, and the pathway target fork-head box protein (FOXO)-1A, while the transcript ..
  74. Buts J, De Keyser N. Transduction pathways regulating the trophic effects of Saccharomyces boulardii in rat intestinal mucosa. Scand J Gastroenterol. 2010;45:175-85 pubmed publisher
    ..boulardii generates in vivo mitogen and metabolic signals that are transduced into intestinal mucosal cells, downstream from the apical membrane to the nuclei, using recruitment substrates and serine, threonine, or tyrosine kinases. ..
  75. Wu L, Liu W, Bayaer N, Gu W, Song J. Exogenous leptin administered intramuscularly induces sex hormone disorder and Ca loss via downregulation of Gnrh and PI3K expression. Exp Anim. 2014;63:447-57 pubmed
    ..The downregulation of PI3K and Gnrh may be involved in the development of this animal model. ..
  76. Qiu J, Ni Y, Chen R, Ji C, Liu F, Zhang C, et al. Gene expression profiles of adipose tissue of obese rats after central administration of neuropeptide Y-Y5 receptor antisense oligodeoxynucleotides by cDNA microarrays. Peptides. 2008;29:2052-60 pubmed publisher
    ..such as FXR1, PHLDA1, MAEA, PIK3R1, ICAM2, PITPN, CALM2, CAMK2D, PKIA, DRD2, SLC25A14, CKB, AADAC, LIPA, ACOX3, FADS1, were concerned...
  77. Cheng S, Ho T, Yang A, Chen I, Kao C, Wu F, et al. Exercise training enhances cardiac IGFI-R/PI3K/Akt and Bcl-2 family associated pro-survival pathways in streptozotocin-induced diabetic rats. Int J Cardiol. 2013;167:478-85 pubmed publisher
    ..Exercise training enhances cardiac IGFI-R/PI3K/Akt and Bcl-2 family associated pro-survival pathways, which provides one of the new beneficial effects for exercise training in diabetes. ..
  78. Nowakowska Zajdel E, Mazurek U, Ziółko E, Niedworok E, Fatyga E, Kokot T, et al. Analysis of expression profile of gene encoding proteins of signal cascades activated by insulin-like growth factors in colorectal cancer. Int J Immunopathol Pharmacol. 2011;24:781-7 pubmed
    ..Among the genes participating in the cascade of signal transfer in cells activated by IGF, GRB10, PIK3R3, PIK3R1, and IRS1 were qualified as differentiating transcripts. IRS1 indicated over-expression in tumour...
  79. Benomar Y, Wetzler S, Larue Achagiotis C, Djiane J, Tom D, Taouis M. In vivo leptin infusion impairs insulin and leptin signalling in liver and hypothalamus. Mol Cell Endocrinol. 2005;242:59-66 pubmed publisher
    ..These results provide evidence that induced hyperleptinemia can contribute to the onset of insulin resistance at least at the hepatic level...
  80. Parborell F, Abramovich D, Irusta G, Tesone M. Angiopoietin 1 reduces rat follicular atresia mediated by apoptosis through the PI3K/Akt pathway. Mol Cell Endocrinol. 2011;343:79-87 pubmed publisher
    ..ANGPT1 may exert these roles by regulating ovarian vascular stability and/or by a direct effect on follicular cells, possibly involving the PI3K/AKT pathway. ..
  81. Reddy V, Valente A, Delafontaine P, Chandrasekar B. Interleukin-18/WNT1-inducible signaling pathway protein-1 signaling mediates human saphenous vein smooth muscle cell proliferation. J Cell Physiol. 2011;226:3303-15 pubmed publisher
  82. Gao F, Hu X, Xie X, Xu Q, Wang Y, Liu X, et al. Heat shock protein 90 protects rat mesenchymal stem cells against hypoxia and serum deprivation-induced apoptosis via the PI3K/Akt and ERK1/2 pathways. J Zhejiang Univ Sci B. 2010;11:608-17 pubmed publisher
    ..These findings demonstrated a novel and effective treatment strategy against MSC apoptosis in cell transplantation. ..
  83. Ferrand A, Kowalski Chauvel A, Bertrand C, Pradayrol L, Fourmy D, Dufresne M, et al. Involvement of JAK2 upstream of the PI 3-kinase in cell-cell adhesion regulation by gastrin. Exp Cell Res. 2004;301:128-38 pubmed
    ..These results described the involvement of JAK2 in the modulation of cell-cell adhesion in epithelial cells. They support a possible role of JAK2 in the epithelial-mesenchymal transition which occurs during malignant development. ..
  84. Khamzina L, Gruppuso P, Wands J. Insulin signaling through insulin receptor substrate 1 and 2 in normal liver development. Gastroenterology. 2003;125:572-85 pubmed
    ..However, insulin-mediated IRS-1/MAPK cascade activation contributes to growth in the adult. ..