Gene Symbol: Pik3r1
Description: phosphoinositide-3-kinase regulatory subunit 1
Alias: PI3K, p50alpha, p55alpha, p85alpha, phosphatidylinositol 3-kinase regulatory subunit alpha, PI3-kinase subunit p85-alpha, PI3K regulatory subunit alpha, phosphatidylinositol 3-kinase 85 kDa regulatory subunit alpha, phosphatidylinositol 3-kinase, regulatory subunit, polypeptide 1 (p85 alpha)
Species: mouse
Products:     Pik3r1

Top Publications

  1. Fang D, Liu Y. Proteolysis-independent regulation of PI3K by Cbl-b-mediated ubiquitination in T cells. Nat Immunol. 2001;2:870-5 pubmed
    ..The p85 regulatory subunit of phosphatidylinositol 3 kinase (PI3K) was identified as a substrate for Cbl-b...
  2. Geering B, Cutillas P, Nock G, Gharbi S, Vanhaesebroeck B. Class IA phosphoinositide 3-kinases are obligate p85-p110 heterodimers. Proc Natl Acad Sci U S A. 2007;104:7809-14 pubmed
    ..a p110 catalytic subunit (p110alpha, p110beta, or p110delta) bound to any of five distinct regulatory subunits (p85alpha, p85beta, p55gamma, p55alpha, and p50alpha, collectively referred to as "p85s")...
  3. Rabinovsky R, Pochanard P, McNear C, Brachmann S, Duke Cohan J, Garraway L, et al. p85 Associates with unphosphorylated PTEN and the PTEN-associated complex. Mol Cell Biol. 2009;29:5377-88 pubmed publisher
    ..D3 position of phosphoinositide-3,4,5-trisphosphate, thereby negatively regulating the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway...
  4. Suzuki H, Matsuda S, Terauchi Y, Fujiwara M, Ohteki T, Asano T, et al. PI3K and Btk differentially regulate B cell antigen receptor-mediated signal transduction. Nat Immunol. 2003;4:280-6 pubmed
    Phosphoinositide-3 kinase (PI3K) is thought to activate the tyrosine kinase Btk...
  5. Terauchi Y, Matsui J, Kamon J, Yamauchi T, Kubota N, Komeda K, et al. Increased serum leptin protects from adiposity despite the increased glucose uptake in white adipose tissue in mice lacking p85alpha phosphoinositide 3-kinase. Diabetes. 2004;53:2261-70 pubmed
    Mice lacking the p85alpha regulatory subunit of phosphoinositide (PI) 3-kinase (Pik3r1(-/-)) showed increased glucose uptake in white adipose tissue (WAT) and skeletal muscle due to increased phosphatidylinositol (3,4,5)-triphosphate [..
  6. 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...
  7. Ueki K, Fruman D, Brachmann S, Tseng Y, Cantley L, Kahn C. Molecular balance between the regulatory and catalytic subunits of phosphoinositide 3-kinase regulates cell signaling and survival. Mol Cell Biol. 2002;22:965-77 pubmed
    ..of a p110 catalytic subunit and a regulatory subunit, the most common family of which is derived from the p85alpha gene (Pik3r1)...
  8. Mali R, Ramdas B, Ma P, Shi J, Munugalavadla V, Sims E, et al. Rho kinase regulates the survival and transformation of cells bearing oncogenic forms of KIT, FLT3, and BCR-ABL. Cancer Cell. 2011;20:357-69 pubmed publisher
    ..activation of Rho kinase (ROCK) in cells bearing oncogenic forms of KIT, FLT3, and BCR-ABL, which is dependent on PI3K and Rho GTPase...
  9. Fruman D, Snapper S, Yballe C, Davidson L, Yu J, Alt F, et al. Impaired B cell development and proliferation in absence of phosphoinositide 3-kinase p85alpha. Science. 1999;283:393-7 pubmed
    ..The mouse gene encoding the PI3K adapter subunit p85alpha and its splice variants p55alpha and p50alpha was disrupted. Most p85alpha-p55alpha-p50alpha-/- mice die within days after birth...

More Information


  1. Taniguchi C, Tran T, Kondo T, Luo J, Ueki K, Cantley L, et al. Phosphoinositide 3-kinase regulatory subunit p85alpha suppresses insulin action via positive regulation of PTEN. Proc Natl Acad Sci U S A. 2006;103:12093-7 pubmed
    ..Here, we show that mice with a liver-specific deletion of the p85alpha regulatory subunit of PI3K (L-Pik3r1KO) exhibit a paradoxical improvement of hepatic and peripheral insulin ..
  2. Chen D, Mauvais Jarvis F, Bluher M, Fisher S, Jozsi A, Goodyear L, et al. p50alpha/p55alpha phosphoinositide 3-kinase knockout mice exhibit enhanced insulin sensitivity. Mol Cell Biol. 2004;24:320-9 pubmed
    ..In addition to p85alpha and p85beta, insulin-sensitive tissues such as fat, muscle, and liver express the splice variants of the pik3r1 ..
  3. Calautti E, Li J, Saoncella S, Brissette J, Goetinck P. Phosphoinositide 3-kinase signaling to Akt promotes keratinocyte differentiation versus death. J Biol Chem. 2005;280:32856-65 pubmed
    ..We show here that the phosphoinositide 3-kinase (PI3K)/Akt pathway is activated at early stages of mouse keratinocyte differentiation both in culture and in the intact ..
  4. 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
    ..To further understand the role of p85, we examined IGF-1-dependent translocation of p85alpha by using a green fluorescence protein (GFP)-tagged p85alpha (EGFP-p85alpha)...
  5. Mauvais Jarvis F, Ueki K, Fruman D, Hirshman M, Sakamoto K, Goodyear L, et al. Reduced expression of the murine p85alpha subunit of phosphoinositide 3-kinase improves insulin signaling and ameliorates diabetes. J Clin Invest. 2002;109:141-9 pubmed
    ..The major regulatory subunits of PI 3-kinase, p85alpha and its splice variants, are encoded by the Pik3r1 gene...
  6. Brachmann S, Yballe C, Innocenti M, Deane J, Fruman D, Thomas S, et al. Role of phosphoinositide 3-kinase regulatory isoforms in development and actin rearrangement. Mol Cell Biol. 2005;25:2593-606 pubmed
    ..Although embryonic development is not impaired in mice lacking all isoforms of the p85alpha gene (p85alpha-/- p55alpha-/- p50alpha-/-) or in mice lacking the p85beta gene (p85beta-/-) (D. A. Fruman, F...
  7. Luo J, Sobkiw C, Logsdon N, Watt J, Signoretti S, O Connell F, et al. Modulation of epithelial neoplasia and lymphoid hyperplasia in PTEN+/- mice by the p85 regulatory subunits of phosphoinositide 3-kinase. Proc Natl Acad Sci U S A. 2005;102:10238-43 pubmed
    ..Here, we examined the effect of deleting various regulatory subunits of PI3K (p85alpha and p85beta) on epithelial neoplasia and lymphoid hyperplasia in PTEN+/- mice...
  8. Zhang X, Vadas O, Perisic O, Anderson K, Clark J, Hawkins P, et al. Structure of lipid kinase p110?/p85? elucidates an unusual SH2-domain-mediated inhibitory mechanism. Mol Cell. 2011;41:567-78 pubmed publisher
    ..This contrasts with the nSH2 where the pY-binding site itself forms the inhibitory contact. This establishes an unusual mechanism by which p85 SH2 domains contribute to RTK signaling specificities. ..
  9. Munugalavadla V, Sims E, Chan R, Lenz S, Kapur R. Requirement for p85alpha regulatory subunit of class IA PI3K in myeloproliferative disease driven by an activation loop mutant of KIT. Exp Hematol. 2008;36:301-8 pubmed publisher
    ..Previous studies have demonstrated hyperactivation of p85alpha regulatory subunit of class IA phosphatidylinositol-3-kinase (PI3K) in cell lines expressing the activation loop ..
  10. Del Rincon J, Iida K, Gaylinn B, McCurdy C, Leitner J, Barbour L, et al. Growth hormone regulation of p85alpha expression and phosphoinositide 3-kinase activity in adipose tissue: mechanism for growth hormone-mediated insulin resistance. Diabetes. 2007;56:1638-46 pubmed
    ..Genetic disruption of the p85alpha regulatory subunit of PI 3-kinase increases insulin sensitivity, whereas elevated p85alpha levels are associated ..
  11. Fruman D, Cantley L, Carpenter C. Structural organization and alternative splicing of the murine phosphoinositide 3-kinase p85 alpha gene. Genomics. 1996;37:113-21 pubmed
    ..Northern blot analysis of mouse tissues reveals differential expression of full-length and alternatively spliced p85 alpha, with the splice variant most abundant in the liver. ..
  12. Luyendyk J, Schabbauer G, Tencati M, Holscher T, Pawlinski R, Mackman N. Genetic analysis of the role of the PI3K-Akt pathway in lipopolysaccharide-induced cytokine and tissue factor gene expression in monocytes/macrophages. J Immunol. 2008;180:4218-26 pubmed
    ..We used peritoneal exudate cells from Pik3r1-deficient mice, which lack the p85alpha regulatory subunit of PI3K and have reduced PI3K activity, and peritoneal macrophages from PTEN(flox/flox)/..
  13. Foukas L, Claret M, Pearce W, Okkenhaug K, Meek S, Peskett E, et al. Critical role for the p110alpha phosphoinositide-3-OH kinase in growth and metabolic regulation. Nature. 2006;441:366-70 pubmed
    ..These findings demonstrate a critical role for p110alpha in growth factor and metabolic signalling and also suggest an explanation for selective mutation or overexpression of p110alpha in a variety of cancers. ..
  14. 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
    ..the role of PI3K in glucose homeostasis, we generated mice with a targeted disruption of the gene encoding the p85alpha regulatory subunit of PI3K (Pik3r1; refs 3-5)...
  15. Abell K, Bilancio A, Clarkson R, Tiffen P, Altaparmakov A, Burdon T, et al. Stat3-induced apoptosis requires a molecular switch in PI(3)K subunit composition. Nat Cell Biol. 2005;7:392-8 pubmed
    ..Here we show that expression of the PI(3)K regulatory subunits p55alpha and p50alpha is induced by Stat3 during involution...
  16. Munugalavadla V, Vemula S, Sims E, Krishnan S, Chen S, Yan J, et al. The p85alpha subunit of class IA phosphatidylinositol 3-kinase regulates the expression of multiple genes involved in osteoclast maturation and migration. Mol Cell Biol. 2008;28:7182-98 pubmed publisher
    ..subunits of class I(A) phosphatidylinositol 3-kinase (PI3-K) although the expression of the full-length form of p85alpha is most abundant...
  17. Schabbauer G, Luyendyk J, Crozat K, Jiang Z, Mackman N, Bahram S, et al. TLR4/CD14-mediated PI3K activation is an essential component of interferon-dependent VSV resistance in macrophages. Mol Immunol. 2008;45:2790-6 pubmed publisher
    Phosphatidylinositol-3-phosphate kinase (PI3K) has been reported to exhibit anti-inflammatory roles as a negative modulator of the NF-kappaB pathway (MyD88- and Mal-dependent) triggered upon Toll-like receptor (TLR)4 activation by ..
  18. Chagpar R, Links P, Pastor M, Furber L, Hawrysh A, Chamberlain M, et al. Direct positive regulation of PTEN by the p85 subunit of phosphatidylinositol 3-kinase. Proc Natl Acad Sci U S A. 2010;107:5471-6 pubmed publisher
    ..We identify the N-terminal SH3-BH region of p85alpha, absent in the smaller p55alpha and p50alpha isoforms, as the region that mediates PTEN binding and regulation...
  19. Suzuki H, Terauchi Y, Fujiwara M, Aizawa S, Yazaki Y, Kadowaki T, et al. Xid-like immunodeficiency in mice with disruption of the p85alpha subunit of phosphoinositide 3-kinase. Science. 1999;283:390-2 pubmed
    Mice with a targeted gene disruption of p85alpha, a regulatory subunit of phosphoinositide 3-kinase, had impaired B cell development at the pro-B cell stage, reduced numbers of mature B cells and peritoneal CD5+ Ly-1 B cells, reduced B ..
  20. García Z, Silio V, Marqués M, Cortes I, Kumar A, Hernandez C, et al. A PI3K activity-independent function of p85 regulatory subunit in control of mammalian cytokinesis. EMBO J. 2006;25:4740-51 pubmed
    ..We studied the role of p85/p110 phosphoinositide kinase (PI3K) in mammalian cytokinesis. Deletion of the p85alpha regulatory subunit induced cell accumulation in telophase and appearance of binucleated cells, whereas inhibition ..
  21. Munugalavadla V, Sims E, Borneo J, Chan R, Kapur R. Genetic and pharmacologic evidence implicating the p85 alpha, but not p85 beta, regulatory subunit of PI3K and Rac2 GTPase in regulating oncogenic KIT-induced transformation in acute myeloid leukemia and systemic mastocytosis. Blood. 2007;110:1612-20 pubmed
    ..Genetic disruption of p85 alpha, the regulatory subunit of class IA lipid kinase phosphoinositol-3-kinase (PI3K), but not of p85 beta, or genetic disruption of the hematopoietic cell-specific Rho GTPase, Rac2, normalizes ..
  22. 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
    ..of insulin, is composed of a catalytic (p110alpha or p110beta) and regulatory (p85alphaalpha, p85betaalpha or p55alpha) subunit...
  23. 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
    Mice that lack the p85alpha regulatory subunit of phosphatidylinositol-3 kinase (PI3K) are deficient in gastrointestinal and peritoneal mast cells but have dermal mast cells...
  24. Garcon F, Patton D, Emery J, Hirsch E, Rottapel R, Sasaki T, et al. CD28 provides T-cell costimulation and enhances PI3K activity at the immune synapse independently of its capacity to interact with the p85/p110 heterodimer. Blood. 2008;111:1464-71 pubmed
    Activation of PI3K is among the earliest signaling events observed in T cells after conjugate formation with antigen-presenting cells (APCs)...
  25. 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
    ..Here we demonstrate that the p85alpha regulatory subunit of phosphoinositide 3-kinase (PI3K), a key mediator of insulin's metabolic actions, is also ..
  26. Fruman D, Mauvais Jarvis F, Pollard D, Yballe C, Brazil D, Bronson R, et al. Hypoglycaemia, liver necrosis and perinatal death in mice lacking all isoforms of phosphoinositide 3-kinase p85 alpha. Nat Genet. 2000;26:379-82 pubmed
    ..The gene Pik3r1 encodes three proteins (p85 alpha, p55 alpha and p50 alpha) that serve as regulatory subunits of class IA Pi3ks (..
  27. Zhu W, Nelson C. PI3K regulates branch initiation and extension of cultured mammary epithelia via Akt and Rac1 respectively. Dev Biol. 2013;379:235-45 pubmed publisher
    ..Here we examined how signaling downstream of phosphoinositide 3-kinase (PI3K) regulates different steps of mammary branching using three-dimensional culture models of the mammary epithelial ..
  28. Luikart B, Zhang W, Wayman G, Kwon C, Westbrook G, Parada L. Neurotrophin-dependent dendritic filopodial motility: a convergence on PI3K signaling. J Neurosci. 2008;28:7006-12 pubmed publisher
    ..dendritic growth cones and filopodia, mediates filopodial motility, and does so via the phosphoinositide 3 kinase (PI3K) pathway...
  29. Park S, Kim S, Choi H, Rhee Y, Lim S. Fibroblast growth factor 2-induced cytoplasmic asparaginyl-tRNA synthetase promotes survival of osteoblasts by regulating anti-apoptotic PI3K/Akt signaling. Bone. 2009;45:994-1003 pubmed publisher
    ..In addition, NARS-induced protection against apoptosis was abolished by the treatment of PI3K inhibitors, wortmannin and LY294002...
  30. Jackson L, Larson S, Silva S, Rychahou P, Chen L, Qiu S, et al. PI3K/Akt activation is critical for early hepatic regeneration after partial hepatectomy. Am J Physiol Gastrointest Liver Physiol. 2008;294:G1401-10 pubmed publisher
    ..Phosphatidylinositol 3-kinase (PI3K), composed of a p85alpha regulatory and a p110alpha catalytic subunit, participates in multiple cellular processes, including cell growth ..
  31. Chamberlain M, Chan T, Oberg J, Hawrysh A, James K, Saxena A, et al. Disrupted RabGAP function of the p85 subunit of phosphatidylinositol 3-kinase results in cell transformation. J Biol Chem. 2008;283:15861-8 pubmed publisher
    ..The p85alpha subunit of phosphatidylinositol 3-kinase has GTPase-activating protein activity toward Rab5 and Rab4, an activity ..
  32. Cho H, Baek K, Saika S, Jeong M, Yoo J. Snail is required for transforming growth factor-beta-induced epithelial-mesenchymal transition by activating PI3 kinase/Akt signal pathway. Biochem Biophys Res Commun. 2007;353:337-43 pubmed
    ..In this report, we suggest phosphatidylinositol 3-OH kinase (PI3K)/Akt signaling is also necessary for TGF-beta-induced EMT in lens epithelial cells by showing that LY294002, an ..
  33. Takai S, Tokuda H, Hanai Y, Kozawa O. Phosphatidylinositol 3-kinase/Akt plays a part in tumor necrosis factor-alpha-induced interleukin-6 synthesis in osteoblasts. Horm Metab Res. 2006;38:563-9 pubmed
    ..These results strongly suggest that PI3-kinase/Akt plays a role in the TNF-alpha-stimulated IL-6 synthesis mainly independent of p44/p42 MAP kinase in osteoblasts. ..
  34. Lindmo K, Stenmark H. Regulation of membrane traffic by phosphoinositide 3-kinases. J Cell Sci. 2006;119:605-14 pubmed
    ..By contrast, class III PI 3-kinases mainly mediate receptor-independent trafficking events, which mostly are related to endocytic membrane traffic, phagosome maturation and autophagy. ..
  35. Zhu S, Sun F, Li W, Cao Y, Wang C, Wang Y, et al. Apelin stimulates glucose uptake through the PI3K/Akt pathway and improves insulin resistance in 3T3-L1 adipocytes. Mol Cell Biochem. 2011;353:305-13 pubmed publisher
    ..Furthermore, apelin pre-incubation also increased adipocytes' insulin-stimulated glucose uptake, and PI3K/Akt pathway were involved in these effects...
  36. Hess K, Donahue A, Ng K, Moore T, Oak J, Fruman D. Frontline: The p85alpha isoform of phosphoinositide 3-kinase is essential for a subset of B cell receptor-initiated signaling responses. Eur J Immunol. 2004;34:2968-76 pubmed
    ..B cell receptor (BCR)-driven proliferation is completely blocked either in cells lacking the p85alpha regulatory isoform of PI3K or in wild-type cells treated with pharmacological PI3K inhibitors...
  37. Hazeki K, Kametani Y, Murakami H, Uehara M, Ishikawa Y, Nigorikawa K, et al. Phosphoinositide 3-kinase? controls the intracellular localization of CpG to limit DNA-PKcs-dependent IL-10 production in macrophages. PLoS ONE. 2011;6:e26836 pubmed publisher
    ..Phosphoinositide 3-kinase (PI3K) has been implicated in CpG-induced immune activation; however, its precise role has not yet been clarified...
  38. Hinoi E, Iezaki T, Fujita H, Watanabe T, Odaka Y, Ozaki K, et al. PI3K/Akt is involved in brown adipogenesis mediated by growth differentiation factor-5 in association with activation of the Smad pathway. Biochem Biophys Res Commun. 2014;450:255-60 pubmed publisher
    ..Here, we show the involvement of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in brown adipogenesis mediated by GDF5...
  39. Veilleux A, Houde V, Bellmann K, Marette A. Chronic inhibition of the mTORC1/S6K1 pathway increases insulin-induced PI3K activity but inhibits Akt2 and glucose transport stimulation in 3T3-L1 adipocytes. Mol Endocrinol. 2010;24:766-78 pubmed publisher
    ..phosphorylate insulin receptor substrate (IRS)-1 on serine residues, which blunts phosphatidylinositol 3-kinase (PI3K) activation...
  40. Yu L, Zhou X, Yu J, Huang H, Jiang L, Zhang F, et al. PI3K contributed to modulation of spinal nociceptive information related to ephrinBs/EphBs. PLoS ONE. 2012;7:e40930 pubmed publisher
    ..In the present study, we investigated whether phosphatidylinositol 3-kinase (PI3K), as the downstream effectors, participates in modulation of spinal nociceptive information related to ephrinBs/..
  41. Shiota M, Kusakabe H, Izumi Y, Hikita Y, Nakao T, Funae Y, et al. Heat shock cognate protein 70 is essential for Akt signaling in endothelial function. Arterioscler Thromb Vasc Biol. 2010;30:491-7 pubmed publisher
    ..Collectively, Hsc70 plays a significant role in ECs via the phosphatidylinositol 3-kinase/Akt pathway. Hsc70 may provide the basis for the development of new therapeutic strategies for angiogenesis. ..
  42. Chen Y, Wang Y, Xie Z, Ming X, Li Z, Kong Y. A tryptophan derivative TD-26 attenuates thrombus formation by inhibiting both PI3K/Akt signaling and binding of fibrinogen to integrin αIIbβ3. Biochem Biophys Res Commun. 2015;465:516-22 pubmed publisher
    ..to integrin αIIbβ3 and reduced Akt(Ser473) phosphorylation in platelet phosphatidylinositol 3-kinase (PI3K) signaling. Furthermore, TD-26 exhibited potent antithrombotic activity in vivo...
  43. Ricort J, Tanti J, Van Obberghen E, Le Marchand Brustel Y. Different effects of insulin and platelet-derived growth factor on phosphatidylinositol 3-kinase at the subcellular level in 3T3-L1 adipocytes. A possible explanation for their specific effects on glucose transport. Eur J Biochem. 1996;239:17-22 pubmed
  44. Kurebayashi Y, Baba Y, Minowa A, Nadya N, Azuma M, Yoshimura A, et al. TGF-?-induced phosphorylation of Akt and Foxo transcription factors negatively regulates induced regulatory T cell differentiation. Biochem Biophys Res Commun. 2016;480:114-119 pubmed publisher
    ..On the other hand, the function of Foxo transcription factors is negatively regulated by PI3K/Akt signaling, which is activated by TGF-? in many types of cells; yet the role of TGF-? in Akt activity and its ..
  45. Matsuda S, Mikami Y, Ohtani M, Fujiwara M, Hirata Y, Minowa A, et al. Critical role of class IA PI3K for c-Rel expression in B lymphocytes. Blood. 2009;113:1037-44 pubmed publisher
    ..We demonstrate here that the Xid mutation renders the Btk protein unstable. Furthermore, class IA PI3K- and Btk-deficient mice show different phenotypes in B-cell development, collectively indicating that PI3Ks and Btk ..
  46. Ozaki M. [Role of jak/STAT3 and PI3-K/Akt pathways in liver injury and regeneration]. Seikagaku. 2008;80:399-408 pubmed
  47. Feutz A, Barrandon Y, Monard D. Control of thrombin signaling through PI3K is a mechanism underlying plasticity between hair follicle dermal sheath and papilla cells. J Cell Sci. 2008;121:1435-43 pubmed publisher
    ..Here, we show that thrombin induces a phosphoinositide 3-kinase (PI3K)-Akt pathway-dependent acquisition of DS-like properties by DP cells in vitro, involving increased proliferation ..
  48. Schaeper U, Gehring N, Fuchs K, Sachs M, Kempkes B, Birchmeier W. Coupling of Gab1 to c-Met, Grb2, and Shp2 mediates biological responses. J Cell Biol. 2000;149:1419-32 pubmed
    ..Overexpression of a Gab1 mutant deficient in Shp2 interaction could also block HGF/SF-induced activation of the MAPK pathway, suggesting that Shp2 is critical for c-Met/Gab1-specific signaling. ..
  49. Winnay J, Dirice E, Liew C, Kulkarni R, Kahn C. p85? deficiency protects ?-cells from endoplasmic reticulum stress-induced apoptosis. Proc Natl Acad Sci U S A. 2014;111:1192-7 pubmed publisher
    ..We identified a role for the p85? regulatory subunit of PI3K to modulate the UPR by promoting the nuclear localization of X-box binding protein 1, a transcription factor ..
  50. A S, Bansal K, Holla S, Verma Kumar S, Sharma P, Balaji K. ESAT-6 induced COX-2 expression involves coordinated interplay between PI3K and MAPK signaling. Mol Immunol. 2012;49:655-63 pubmed publisher
    ..Signaling perturbation data suggest that signaling dynamics of PI3K and p38 and JNK1/2 MAPK assume critical importance in ESAT-6 triggered expression of COX-2 in macrophages...
  51. Jagarlamudi K, Liu L, Adhikari D, Reddy P, Idahl A, Ottander U, et al. Oocyte-specific deletion of Pten in mice reveals a stage-specific function of PTEN/PI3K signaling in oocytes in controlling follicular activation. PLoS ONE. 2009;4:e6186 pubmed publisher
    ..Recently, it was found that overactivation of the phosphatidylinositol 3-kinase (PI3K) signaling in oocytes of primordial follicles by an oocyte-specific deletion of Pten (phosphatase and tensin ..
  52. Laird M, Rhee S, Perkins D, Medvedev A, Piao W, Fenton M, et al. TLR4/MyD88/PI3K interactions regulate TLR4 signaling. J Leukoc Biol. 2009;85:966-77 pubmed publisher
    ..TLR4-mediated signaling also leads to rapid activation of PI3K, one of a family of kinases involved in regulation of cell growth, apoptosis, and motility...
  53. Piquer S, Barceló Batllori S, Julià M, Marzo N, Nadal B, Guinovart J, et al. Phosphorylation events implicating p38 and PI3K mediate tungstate-effects in MIN6 beta cells. Biochem Biophys Res Commun. 2007;358:385-91 pubmed
    ..Tungstate treatment induced phosphorylation and subsequent activation of p38 and PI3K which in turn are implicated in tungstate PDX-1 nuclear localization and activation...
  54. Arbuckle M, Komiyama N, Delaney A, Coba M, Garry E, Rosie R, et al. The SH3 domain of postsynaptic density 95 mediates inflammatory pain through phosphatidylinositol-3-kinase recruitment. EMBO Rep. 2010;11:473-8 pubmed publisher
    ..These results show that different types of behavioural plasticity are mediated by specific domains of PSD95 and suggest novel therapeutic avenues for reducing inflammatory pain. ..
  55. Li Q, Hata A, Kosugi C, Kataoka N, Funaki M. The density of extracellular matrix proteins regulates inflammation and insulin signaling in adipocytes. FEBS Lett. 2010;584:4145-50 pubmed publisher
    ..These results indicate that the density of the ECM directly regulates the inflammatory response and insulin sensitivity of adipocytes. ..
  56. Xie Z, Xin G, Xu Y, Su Y, Li K. LPS-Primed Release of HMGB-1 from Cortical Astrocytes is Modulated Through PI3K/AKT Pathway. Cell Mol Neurobiol. 2016;36:93-102 pubmed publisher
    ..Furthermore, a potential cellular pathway (PI3K/AKT pathway), has been proposed for the active regulation of LPS-primed reactive astrocytes to secrete HMGB-1...
  57. Leavenworth J, Verbinnen B, Yin J, Huang H, Cantor H. A p85α-osteopontin axis couples the receptor ICOS to sustained Bcl-6 expression by follicular helper and regulatory T cells. Nat Immunol. 2015;16:96-106 pubmed publisher
  58. Hunter S, Burton E, Wu S, Anderson S. Fyn associates with Cbl and phosphorylates tyrosine 731 in Cbl, a binding site for phosphatidylinositol 3-kinase. J Biol Chem. 1999;274:2097-106 pubmed
  59. Cohran V, Managlia E, Bradford E, Goretsky T, Li T, Katzman R, et al. Epithelial PIK3R1 (p85) and TP53 Regulate Survivin Expression during Adaptation to Ileocecal Resection. Am J Pathol. 2016;186:1837-1846 pubmed publisher
    ..Wild-type and epithelial Pik3r1 (p85?)-deficient mice underwent sham surgery or 30% resection...
  60. Wakayama S, Haque A, Koide N, Kato Y, Odkhuu E, Bilegtsaikhan T, et al. Lipopolysaccharide impairs insulin sensitivity via activation of phosphoinositide 3-kinase in adipocytes. Immunopharmacol Immunotoxicol. 2014;36:145-9 pubmed publisher
    ..LPS-induced activation of phosphoinositide 3-kinase (PI3K) in adipocytes...
  61. Lu Z, Jiang Y, Ballou L, Cohen I, Lin R. Galpha q inhibits cardiac L-type Ca2+ channels through phosphatidylinositol 3-kinase. J Biol Chem. 2005;280:40347-54 pubmed
    ..By contrast, PI 4,5-bisphosphate (PI(4,5)P2) or PI 3,5-bisphosphate had no effect. Infusion with p110beta/p85alpha or p110gamma PI3K in the presence of PI(4,5)P2 also restored I(Ca,L) density to wild-type levels...
  62. Lien S, Usami S, Chien S, Chiu J. Phosphatidylinositol 3-kinase/Akt pathway is involved in transforming growth factor-beta1-induced phenotypic modulation of 10T1/2 cells to smooth muscle cells. Cell Signal. 2006;18:1270-8 pubmed
    ..we examined the role of the mitogen-activated protein kinase (MAPK) superfamily and phosphatidylinositol 3-kinase (PI3K)/Akt in the TGF-beta1-mediated phenotypic modulation of 10T1/2 mesenchymal cells to SMCs characterized by the ..
  63. Deane J, Kharas M, Oak J, Stiles L, Luo J, Moore T, et al. T-cell function is partially maintained in the absence of class IA phosphoinositide 3-kinase signaling. Blood. 2007;109:2894-902 pubmed
    ..we analyze conditional mutant mice in which thymocytes and T cells lack the major class IA regulatory subunits p85alpha, p55alpha, p50alpha, and p85beta...
  64. Watanabe H, Saito H, Nishimura H, Ueda J, Evers B. Activation of phosphatidylinositol-3 kinase regulates pancreatic duodenal homeobox-1 in duct cells during pancreatic regeneration. Pancreas. 2008;36:153-9 pubmed publisher
    The purpose of our study was to determine whether the phosphatidylinositol 3-kinase (PI3K)/Akt pathway contributes to expression of pancreatic duodenal homeobox-1 (PDX-1) in duct cells and the cell differentiation during pancreatic ..
  65. de Oliveira M, Luvizotto R, Olímpio R, de Síbio M, Conde S, Biz Rodrigues Silva C, et al. Triiodothyronine increases mRNA and protein leptin levels in short time in 3T3-L1 adipocytes by PI3K pathway activation. PLoS ONE. 2013;8:e74856 pubmed publisher
    ..T3), on the modulation of leptin mRNA expression and the involvement of the phosphatidyl inositol 3 kinase (PI3K) signaling pathway in adipocytes, 3T3-L1, cell culture...
  66. Ikegami D, Akiyama H, Suzuki A, Nakamura T, Nakano T, Yoshikawa H, et al. Sox9 sustains chondrocyte survival and hypertrophy in part through Pik3ca-Akt pathways. Development. 2011;138:1507-19 pubmed publisher
    ..When the molecular mechanism of Sox9-induced Akt phosphorylation was examined, we found that expression of the PI3K subunit Pik3ca (p110?) was decreased in Sox9(floxdel/floxdel) mouse chondrocytes...
  67. Chanprasert S, Geddis A, Barroga C, Fox N, Kaushansky K. Thrombopoietin (TPO) induces c-myc expression through a PI3K- and MAPK-dependent pathway that is not mediated by Akt, PKCzeta or mTOR in TPO-dependent cell lines and primary megakaryocytes. Cell Signal. 2006;18:1212-8 pubmed
    ..TPO signals through the Jak-STAT, Ras-Raf-MAPK, and PI3K pathways, and promotes survival, proliferation, and polyploidization in megakaryocytes...
  68. Doi T, Obayashi K, Kadowaki T, Fujii H, Koyasu S. PI3K is a negative regulator of IgE production. Int Immunol. 2008;20:499-508 pubmed publisher
    ..We found that mice deficient for the p85alpha regulatory subunit of class IA phosphoinositide 3-kinase (PI3K) produced increasing amounts of serum IgE...
  69. Harrington L, Findlay G, Gray A, Tolkacheva T, Wigfield S, Rebholz H, et al. The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins. J Cell Biol. 2004;166:213-23 pubmed
    Insulin-like growth factors elicit many responses through activation of phosphoinositide 3-OH kinase (PI3K)...
  70. Thomas M, Mills J, Engelbrecht A. Phosphatidylinositol-3-kinase (PI3K) activity decreases in C2C12 myotubes during acute simulated ischemia at a cost to their survival. Life Sci. 2012;91:44-53 pubmed publisher
    ..Therefore, we aimed to determine the role of the PI3K signaling pathway during acute SI in C2C12 myotubes and analyze the related impact on cell death parameters ..
  71. Wilson E, Tureckova J, Rotwein P. Permissive roles of phosphatidyl inositol 3-kinase and Akt in skeletal myocyte maturation. Mol Biol Cell. 2004;15:497-505 pubmed
  72. Krebs D, Uren R, Metcalf D, Rakar S, Zhang J, Starr R, et al. SOCS-6 binds to insulin receptor substrate 4, and mice lacking the SOCS-6 gene exhibit mild growth retardation. Mol Cell Biol. 2002;22:4567-78 pubmed
    ..However, both male and female SOCS-6(-/-) mice weighed approximately 10% less than wild-type littermates. ..
  73. Dygai A, Zhdanov V, Miroshnichenko L, Udut E, Zyuz kov G, Simanina E, et al. Role of PI3K, MAPK/ERK1/2, and p38 in implementation of the proliferative and differentiation potential of erythroid progenitors after blood loss. Bull Exp Biol Med. 2015;158:417-20 pubmed publisher
    The involvement of PI3K, ERK and p38-dependent signaling system in the regulation of functional activity of erythroid precursors after blood loss (30% of circulating volume) was studied...
  74. Shinohara M, Nakamura M, Masuda H, Hirose J, Kadono Y, Iwasawa M, et al. Class IA phosphatidylinositol 3-kinase regulates osteoclastic bone resorption through protein kinase B-mediated vesicle transport. J Bone Miner Res. 2012;27:2464-75 pubmed publisher
    ..The physiological relevance of the in vitro studies using PI3K inhibitors has been of limited value, because they inhibit all classes of PI3K...
  75. Iwanishi M. Overexpression of Fer increases the association of tyrosine-phosphorylated IRS-1 with P85 phosphatidylinositol kinase via SH2 domain of Fer in transfected cells. Biochem Biophys Res Commun. 2003;311:780-5 pubmed
    ..Taken together, these data suggested that Fer may play a critically important role to form Fer/IRS-1/P85 complex in LDM of insulin-stimulated adipocytes and elicit biological effect through PI-3 kinase activity in LDM. ..