NamePhosphatidylinositol 3-kinase regulatory subunit alpha
Synonyms
  • GRB1
  • Phosphatidylinositol 3-kinase 85 kDa regulatory subunit alpha
  • PI3-kinase regulatory subunit alpha
  • PI3-kinase subunit p85-alpha
  • PtdIns-3-kinase regulatory subunit p85-alpha
Gene NamePIK3R1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0001901|Phosphatidylinositol 3-kinase regulatory subunit alpha
MSAEGYQYRALYDYKKEREEDIDLHLGDILTVNKGSLVALGFSDGQEARPEEIGWLNGYN
ETTGERGDFPGTYVEYIGRKKISPPTPKPRPPRPLPVAPGSSKTEADVEQQALTLPDLAE
QFAPPDIAPPLLIKLVEAIEKKGLECSTLYRTQSSSNLAELRQLLDCDTPSVDLEMIDVH
VLADAFKRYLLDLPNPVIPAAVYSEMISLAPEVQSSEEYIQLLKKLIRSPSIPHQYWLTL
QYLLKHFFKLSQTSSKNLLNARVLSEIFSPMLFRFSAASSDNTENLIKVIEILISTEWNE
RQPAPALPPKPPKPTTVANNGMNNNMSLQDAEWYWGDISREEVNEKLRDTADGTFLVRDA
STKMHGDYTLTLRKGGNNKLIKIFHRDGKYGFSDPLTFSSVVELINHYRNESLAQYNPKL
DVKLLYPVSKYQQDQVVKEDNIEAVGKKLHEYNTQFQEKSREYDRLYEEYTRTSQEIQMK
RTAIEAFNETIKIFEEQCQTQERYSKEYIEKFKREGNEKEIQRIMHNYDKLKSRISEIID
SRRRLEEDLKKQAAEYREIDKRMNSIKPDLIQLRKTRDQYLMWLTQKGVRQKKLNEWLGN
ENTEDQYSLVEDDEDLPHHDEKTWNVGSSNRNKAENLLRGKRDGTFLVRESSKQGCYACS
VVVDGEVKHCVINKTATGYGFAEPYNLYSSLKELVLHYQHTSLVQHNDSLNVTLAYPVYA
QQRR
Number of residues724
Molecular Weight83597.675
Theoretical pI6.06
GO Classification
Functions
  • insulin-like growth factor receptor binding
  • phosphatidylinositol 3-kinase binding
  • transmembrane receptor protein tyrosine kinase adaptor activity
  • phosphatidylinositol 3-kinase regulator activity
  • protein phosphatase binding
  • insulin binding
  • 1-phosphatidylinositol-3-kinase regulator activity
  • neurotrophin TRKA receptor binding
  • transcription factor binding
  • ErbB-3 class receptor binding
  • insulin receptor binding
  • insulin receptor substrate binding
Processes
  • phosphatidylinositol-mediated signaling
  • epidermal growth factor receptor signaling pathway
  • positive regulation of establishment of protein localization to plasma membrane
  • extrinsic apoptotic signaling pathway via death domain receptors
  • phospholipid metabolic process
  • Fc-gamma receptor signaling pathway involved in phagocytosis
  • regulation of stress fiber assembly
  • innate immune response
  • cellular response to UV
  • T cell costimulation
  • intrinsic apoptotic signaling pathway in response to DNA damage
  • positive regulation of glucose import
  • positive regulation of endoplasmic reticulum unfolded protein response
  • T cell receptor signaling pathway
  • Fc-epsilon receptor signaling pathway
  • positive regulation of glucose import in response to insulin stimulus
  • positive regulation of transcription factor import into nucleus
  • positive regulation of RNA splicing
  • leukocyte migration
  • phosphatidylinositol phosphorylation
  • protein stabilization
  • response to endoplasmic reticulum stress
  • positive regulation of cell migration
  • phosphatidylinositol biosynthetic process
  • fibroblast growth factor receptor signaling pathway
  • negative regulation of cell-matrix adhesion
  • blood coagulation
  • growth hormone receptor signaling pathway
  • insulin receptor signaling pathway
  • NFAT protein import into nucleus
  • insulin-like growth factor receptor signaling pathway
  • negative regulation of apoptotic process
  • neurotrophin TRK receptor signaling pathway
  • viral process
  • positive regulation of transcription from RNA polymerase II promoter
  • protein phosphorylation
  • regulation of phosphatidylinositol 3-kinase activity
  • phosphatidylinositol 3-kinase signaling
  • vascular endothelial growth factor receptor signaling pathway
  • platelet activation
  • B cell differentiation
  • positive regulation of tumor necrosis factor production
  • small molecule metabolic process
  • cellular glucose homeostasis
  • cellular response to insulin stimulus
  • negative regulation of osteoclast differentiation
Components
  • cell-cell junction
  • perinuclear endoplasmic reticulum membrane
  • cytoplasm
  • membrane
  • cis-Golgi network
  • phosphatidylinositol 3-kinase complex
  • nucleus
  • phosphatidylinositol 3-kinase complex, class IA
  • plasma membrane
  • cytosol
General FunctionTransmembrane receptor protein tyrosine kinase adaptor activity
Specific FunctionBinds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling (PubMed:17626883, PubMed:19805105, PubMed:7518429). Modulates the cellular response to ER stress by promoting nuclear translocation of XBP1 isoform 2 in a ER stress-and/or insulin-dependent manner during metabolic overloading in the liver and hence plays a role in glucose tolerance improvement (PubMed:20348923).
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDP27986
UniProtKB Entry NameP85A_HUMAN
Cellular LocationCytoplasmic
Gene sequence
>lcl|BSEQ0021657|Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1)
ATGCATGGTGATTATACTCTTACACTAAGGAAAGGGGGAAATAACAAATTAATCAAAATA
TTTCATCGAGATGGGAAATATGGCTTCTCTGACCCATTAACCTTCAGTTCTGTGGTTGAA
TTAATAAACCACTACCGGAATGAATCTCTAGCTCAGTATAATCCCAAATTGGATGTGAAA
TTACTTTATCCAGTATCCAAATACCAACAGGATCAAGTTGTCAAAGAAGATAATATTGAA
GCTGTAGGGAAAAAATTACATGAATATAACACTCAGTTTCAAGAAAAAAGTCGAGAATAT
GATAGATTATATGAAGAATATACCCGCACATCCCAGGAAATCCAAATGAAAAGGACAGCT
ATTGAAGCATTTAATGAAACCATAAAAATATTTGAAGAACAGTGCCAGACCCAAGAGCGG
TACAGCAAAGAATACATAGAAAAGTTTAAACGTGAAGGCAATGAGAAAGAAATACAAAGG
ATTATGCATAATTATGATAAGTTGAAGTCTCGAATCAGTGAAATTATTGACAGTAGAAGA
AGATTGGAAGAAGACTTGAAGAAGCAGGCAGCTGAGTATCGAGAAATTGACAAACGTATG
AACAGCATTAAACCAGACCTTATCCAGCTGAGAAAGACGAGAGACCAATACTTGATGTGG
TTGACTCAAAAAGGTGTTCGGCAAAAGAAGTTGAACGAGTGGTTGGGCAATGAAAACACT
GAAGACCAATATTCACTGGTGGAAGATGATGAAGATTTGCCCCATCATGATGAGAAGACA
TGGAATGTTGGAAGCAGCAACCGAAACAAAGCTGAAAACCTGTTGCGAGGGAAGCGAGAT
GGCACTTTTCTTGTCCGGGAGAGCAGTAAACAGGGCTGCTATGCCTGCTCTGTAGTGGTG
GACGGCGAAGTAAAGCATTGTGTCATAAACAAAACAGCAACTGGCTATGGCTTTGCCGAG
CCCTATAACTTGTACAGCTCTCTGAAAGAACTGGTGCTACATTACCAACACACCTCCCTT
GTGCAGCACAACGACTCCCTCAATGTCACACTAGCCTACCCAGTATATGCACAGCAGAGG
CGATGA
GenBank Gene IDM61906
GeneCard IDNot Available
GenAtlas IDPIK3R1
HGNC IDHGNC:8979
Chromosome Location5
Locus5q13.1
References
  1. Skolnik EY, Margolis B, Mohammadi M, Lowenstein E, Fischer R, Drepps A, Ullrich A, Schlessinger J: Cloning of PI3 kinase-associated p85 utilizing a novel method for expression/cloning of target proteins for receptor tyrosine kinases. Cell. 1991 Apr 5;65(1):83-90. 1849461
  2. Antonetti DA, Algenstaedt P, Kahn CR: 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 May;16(5):2195-203. 8628286
  3. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  4. Schmutz J, Martin J, Terry A, Couronne O, Grimwood J, Lowry S, Gordon LA, Scott D, Xie G, Huang W, Hellsten U, Tran-Gyamfi M, She X, Prabhakar S, Aerts A, Altherr M, Bajorek E, Black S, Branscomb E, Caoile C, Challacombe JF, Chan YM, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Lopez F, Lou Y, Martinez D, Medina C, Morgan J, Nandkeshwar R, Noonan JP, Pitluck S, Pollard M, Predki P, Priest J, Ramirez L, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wheeler J, Wu K, Yang J, Dickson M, Cheng JF, Eichler EE, Olsen A, Pennacchio LA, Rokhsar DS, Richardson P, Lucas SM, Myers RM, Rubin EM: The DNA sequence and comparative analysis of human chromosome 5. Nature. 2004 Sep 16;431(7006):268-74. 15372022
  5. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  6. Nishimura R, Li W, Kashishian A, Mondino A, Zhou M, Cooper J, Schlessinger J: Two signaling molecules share a phosphotyrosine-containing binding site in the platelet-derived growth factor receptor. Mol Cell Biol. 1993 Nov;13(11):6889-96. 7692233
  7. Van Horn DJ, Myers MG Jr, Backer JM: Direct activation of the phosphatidylinositol 3'-kinase by the insulin receptor. J Biol Chem. 1994 Jan 7;269(1):29-32. 8276809
  8. Vainikka S, Joukov V, Wennstrom S, Bergman M, Pelicci PG, Alitalo K: Signal transduction by fibroblast growth factor receptor-4 (FGFR-4). Comparison with FGFR-1. J Biol Chem. 1994 Jul 15;269(28):18320-6. 7518429
  9. Craparo A, O'Neill TJ, Gustafson TA: 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 Jun 30;270(26):15639-43. 7541045
  10. Gustafson TA, He W, Craparo A, Schaub CD, O'Neill TJ: 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 May;15(5):2500-8. 7537849
  11. Yokote K, Margolis B, Heldin CH, Claesson-Welsh L: Grb7 is a downstream signaling component of platelet-derived growth factor alpha- and beta-receptors. J Biol Chem. 1996 Nov 29;271(48):30942-9. 8940081
  12. Price DJ, Rivnay B, Fu Y, Jiang S, Avraham S, Avraham H: Direct association of Csk homologous kinase (CHK) with the diphosphorylated site Tyr568/570 of the activated c-KIT in megakaryocytes. J Biol Chem. 1997 Feb 28;272(9):5915-20. 9038210
  13. Braunger J, Schleithoff L, Schulz AS, Kessler H, Lammers R, Ullrich A, Bartram CR, Janssen JW: Intracellular signaling of the Ufo/Axl receptor tyrosine kinase is mediated mainly by a multi-substrate docking-site. Oncogene. 1997 Jun 5;14(22):2619-31. 9178760
  14. Zhang W, Sloan-Lancaster J, Kitchen J, Trible RP, Samelson LE: LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation. Cell. 1998 Jan 9;92(1):83-92. 9489702
  15. Fantin VR, Sparling JD, Slot JW, Keller SR, Lienhard GE, Lavan BE: Characterization of insulin receptor substrate 4 in human embryonic kidney 293 cells. J Biol Chem. 1998 Apr 24;273(17):10726-32. 9553137
  16. Bruyns E, Marie-Cardine A, Kirchgessner H, Sagolla K, Shevchenko A, Mann M, Autschbach F, Bensussan A, Meuer S, Schraven B: T cell receptor (TCR) interacting molecule (TRIM), a novel disulfide-linked dimer associated with the TCR-CD3-zeta complex, recruits intracellular signaling proteins to the plasma membrane. J Exp Med. 1998 Aug 3;188(3):561-75. 9687533
  17. Chang C, Dietrich J, Harpur AG, Lindquist JA, Haude A, Loke YW, King A, Colonna M, Trowsdale J, Wilson MJ: Cutting edge: KAP10, a novel transmembrane adapter protein genetically linked to DAP12 but with unique signaling properties. J Immunol. 1999 Nov 1;163(9):4651-4. 10528161
  18. Ettenberg SA, Keane MM, Nau MM, Frankel M, Wang LM, Pierce JH, Lipkowitz S: cbl-b inhibits epidermal growth factor receptor signaling. Oncogene. 1999 Mar 11;18(10):1855-66. 10086340
  19. Axelsson L, Hellberg C, Melander F, Smith D, Zheng L, Andersson T: Clustering of beta(2)-integrins on human neutrophils activates dual signaling pathways to PtdIns 3-kinase. Exp Cell Res. 2000 Apr 10;256(1):257-63. 10739672
  20. Sweeney C, Lai C, Riese DJ 2nd, Diamonti AJ, Cantley LC, Carraway KL 3rd: Ligand discrimination in signaling through an ErbB4 receptor homodimer. J Biol Chem. 2000 Jun 30;275(26):19803-7. 10867024
  21. Fang D, Wang HY, Fang N, Altman Y, Elly C, Liu YC: Cbl-b, a RING-type E3 ubiquitin ligase, targets phosphatidylinositol 3-kinase for ubiquitination in T cells. J Biol Chem. 2001 Feb 16;276(7):4872-8. Epub 2000 Nov 21. 11087752
  22. Fang D, Liu YC: Proteolysis-independent regulation of PI3K by Cbl-b-mediated ubiquitination in T cells. Nat Immunol. 2001 Sep;2(9):870-5. 11526404
  23. Sano H, Liu SC, Lane WS, Piletz JE, Lienhard GE: Insulin receptor substrate 4 associates with the protein IRAS. J Biol Chem. 2002 May 31;277(22):19439-47. Epub 2002 Mar 23. 11912194
  24. Zhu M, Janssen E, Leung K, Zhang W: Molecular cloning of a novel gene encoding a membrane-associated adaptor protein (LAX) in lymphocyte signaling. J Biol Chem. 2002 Nov 29;277(48):46151-8. Epub 2002 Sep 30. 12359715
  25. Linnemann T, Zheng YH, Mandic R, Peterlin BM: Interaction between Nef and phosphatidylinositol-3-kinase leads to activation of p21-activated kinase and increased production of HIV. Virology. 2002 Mar 15;294(2):246-55. 12009866
  26. He Y, Nakao H, Tan SL, Polyak SJ, Neddermann P, Vijaysri S, Jacobs BL, Katze MG: Subversion of cell signaling pathways by hepatitis C virus nonstructural 5A protein via interaction with Grb2 and P85 phosphatidylinositol 3-kinase. J Virol. 2002 Sep;76(18):9207-17. 12186904
  27. Tacconelli A, Farina AR, Cappabianca L, Desantis G, Tessitore A, Vetuschi A, Sferra R, Rucci N, Argenti B, Screpanti I, Gulino A, Mackay AR: TrkA alternative splicing: a regulated tumor-promoting switch in human neuroblastoma. Cancer Cell. 2004 Oct;6(4):347-60. 15488758
  28. Ronnstrand L: Signal transduction via the stem cell factor receptor/c-Kit. Cell Mol Life Sci. 2004 Oct;61(19-20):2535-48. 15526160
  29. Laurent CE, Smithgall TE: The c-Fes tyrosine kinase cooperates with the breakpoint cluster region protein (Bcr) to induce neurite extension in a Rac- and Cdc42-dependent manner. Exp Cell Res. 2004 Sep 10;299(1):188-98. 15302586
  30. Continolo S, Baruzzi A, Majeed M, Caveggion E, Fumagalli L, Lowell CA, Berton G: The proto-oncogene Fgr regulates cell migration and this requires its plasma membrane localization. Exp Cell Res. 2005 Jan 15;302(2):253-69. 15561106
  31. Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ: Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nat Biotechnol. 2005 Jan;23(1):94-101. Epub 2004 Dec 12. 15592455
  32. Tsuboi N, Utsunomiya T, Roberts RL, Ito H, Takahashi K, Noda M, Takahashi T: The tyrosine phosphatase CD148 interacts with the p85 regulatory subunit of phosphoinositide 3-kinase. Biochem J. 2008 Jul 1;413(1):193-200. doi: 10.1042/BJ20071317. 18348712
  33. Kaushansky A, Gordus A, Budnik BA, Lane WS, Rush J, MacBeath G: System-wide investigation of ErbB4 reveals 19 sites of Tyr phosphorylation that are unusually selective in their recruitment properties. Chem Biol. 2008 Aug 25;15(8):808-17. doi: 10.1016/j.chembiol.2008.07.006. 18721752
  34. Voss M, Lettau M, Janssen O: Identification of SH3 domain interaction partners of human FasL (CD178) by phage display screening. BMC Immunol. 2009 Oct 6;10:53. doi: 10.1186/1471-2172-10-53. 19807924
  35. Salazar L, Kashiwada T, Krejci P, Muchowski P, Donoghue D, Wilcox WR, Thompson LM: A novel interaction between fibroblast growth factor receptor 3 and the p85 subunit of phosphoinositide 3-kinase: activation-dependent regulation of ERK by p85 in multiple myeloma cells. Hum Mol Genet. 2009 Jun 1;18(11):1951-61. doi: 10.1093/hmg/ddp116. Epub 2009 Mar 13. 19286672
  36. Eswarakumar VP, Lax I, Schlessinger J: Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev. 2005 Apr;16(2):139-49. Epub 2005 Feb 1. 15863030
  37. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. 19369195
  38. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. 19690332
  39. Winnay JN, Boucher J, Mori MA, Ueki K, Kahn CR: 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 Apr;16(4):438-45. doi: 10.1038/nm.2121. Epub 2010 Mar 28. 20348923
  40. Wagner MJ, Smiley JR: Herpes simplex virus requires VP11/12 to activate Src family kinase-phosphoinositide 3-kinase-Akt signaling. J Virol. 2011 Mar;85(6):2803-12. doi: 10.1128/JVI.01877-10. Epub 2011 Jan 12. 21228233
  41. Conley ME, Dobbs AK, Quintana AM, Bosompem A, Wang YD, Coustan-Smith E, Smith AM, Perez EE, Murray PJ: Agammaglobulinemia and absent B lineage cells in a patient lacking the p85alpha subunit of PI3K. J Exp Med. 2012 Mar 12;209(3):463-70. doi: 10.1084/jem.20112533. Epub 2012 Feb 20. 22351933
  42. Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi: 10.1073/pnas.1210303109. Epub 2012 Jul 18. 22814378
  43. Dyment DA, Smith AC, Alcantara D, Schwartzentruber JA, Basel-Vanagaite L, Curry CJ, Temple IK, Reardon W, Mansour S, Haq MR, Gilbert R, Lehmann OJ, Vanstone MR, Beaulieu CL, Majewski J, Bulman DE, O'Driscoll M, Boycott KM, Innes AM: Mutations in PIK3R1 cause SHORT syndrome. Am J Hum Genet. 2013 Jul 11;93(1):158-66. doi: 10.1016/j.ajhg.2013.06.005. Epub 2013 Jun 27. 23810382
  44. Liu X, Cohen JI: Varicella-zoster virus ORF12 protein activates the phosphatidylinositol 3-kinase/Akt pathway to regulate cell cycle progression. J Virol. 2013 Feb;87(3):1842-8. doi: 10.1128/JVI.02395-12. Epub 2012 Nov 28. 23192871
  45. Cipriano R, Miskimen KL, Bryson BL, Foy CR, Bartel CA, Jackson MW: FAM83B-mediated activation of PI3K/AKT and MAPK signaling cooperates to promote epithelial cell transformation and resistance to targeted therapies. Oncotarget. 2013 May;4(5):729-38. 23676467
  46. Deau MC, Heurtier L, Frange P, Suarez F, Bole-Feysot C, Nitschke P, Cavazzana M, Picard C, Durandy A, Fischer A, Kracker S: A human immunodeficiency caused by mutations in the PIK3R1 gene. J Clin Invest. 2014 Sep;124(9):3923-8. doi: 10.1172/JCI75746. Epub 2014 Aug 18. 25133428
  47. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. 25944712
  48. Liang J, Chen JK, Schreiber ST, Clardy J: Crystal structure of P13K SH3 domain at 20 angstroms resolution. J Mol Biol. 1996 Apr 5;257(3):632-43. 8648629
  49. Nolte RT, Eck MJ, Schlessinger J, Shoelson SE, Harrison SC: Crystal structure of the PI 3-kinase p85 amino-terminal SH2 domain and its phosphopeptide complexes. Nat Struct Biol. 1996 Apr;3(4):364-74. 8599763
  50. Musacchio A, Cantley LC, Harrison SC: Crystal structure of the breakpoint cluster region-homology domain from phosphoinositide 3-kinase p85 alpha subunit. Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14373-8. 8962058
  51. Pauptit RA, Dennis CA, Derbyshire DJ, Breeze AL, Weston SA, Rowsell S, Murshudov GN: NMR trial models: experiences with the colicin immunity protein Im7 and the p85alpha C-terminal SH2-peptide complex. Acta Crystallogr D Biol Crystallogr. 2001 Oct;57(Pt 10):1397-404. Epub 2001 Sep 21. 11567151
  52. Koyama S, Yu H, Dalgarno DC, Shin TB, Zydowsky LD, Schreiber SL: Structure of the PI3K SH3 domain and analysis of the SH3 family. Cell. 1993 Mar 26;72(6):945-52. 7681364
  53. Renzoni DA, Pugh DJ, Siligardi G, Das P, Morton CJ, Rossi C, Waterfield MD, Campbell ID, Ladbury JE: Structural and thermodynamic characterization of the interaction of the SH3 domain from Fyn with the proline-rich binding site on the p85 subunit of PI3-kinase. Biochemistry. 1996 Dec 10;35(49):15646-53. 8961927
  54. Breeze AL, Kara BV, Barratt DG, Anderson M, Smith JC, Luke RW, Best JR, Cartlidge SA: Structure of a specific peptide complex of the carboxy-terminal SH2 domain from the p85 alpha subunit of phosphatidylinositol 3-kinase. EMBO J. 1996 Jul 15;15(14):3579-89. 8670861
  55. Miled N, Yan Y, Hon WC, Perisic O, Zvelebil M, Inbar Y, Schneidman-Duhovny D, Wolfson HJ, Backer JM, Williams RL: Mechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit. Science. 2007 Jul 13;317(5835):239-42. 17626883
  56. Huang CH, Mandelker D, Schmidt-Kittler O, Samuels Y, Velculescu VE, Kinzler KW, Vogelstein B, Gabelli SB, Amzel LM: The structure of a human p110alpha/p85alpha complex elucidates the effects of oncogenic PI3Kalpha mutations. Science. 2007 Dec 14;318(5857):1744-8. 18079394
  57. Mandelker D, Gabelli SB, Schmidt-Kittler O, Zhu J, Cheong I, Huang CH, Kinzler KW, Vogelstein B, Amzel LM: A frequent kinase domain mutation that changes the interaction between PI3Kalpha and the membrane. Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):16996-7001. doi: 10.1073/pnas.0908444106. Epub 2009 Sep 23. 19805105
  58. Batra-Safferling R, Granzin J, Modder S, Hoffmann S, Willbold D: Structural studies of the phosphatidylinositol 3-kinase (PI3K) SH3 domain in complex with a peptide ligand: role of the anchor residue in ligand binding. Biol Chem. 2010 Jan;391(1):33-42. doi: 10.1515/BC.2010.003. 19919182
  59. Hansen T, Andersen CB, Echwald SM, Urhammer SA, Clausen JO, Vestergaard H, Owens D, Hansen L, Pedersen O: Identification of a common amino acid polymorphism in the p85alpha regulatory subunit of phosphatidylinositol 3-kinase: effects on glucose disappearance constant, glucose effectiveness, and the insulin sensitivity index. Diabetes. 1997 Mar;46(3):494-501. 9032108
  60. Baynes KC, Beeton CA, Panayotou G, Stein R, Soos M, Hansen T, Simpson H, O'Rahilly S, Shepherd PR, Whitehead JP: Natural variants of human p85 alpha phosphoinositide 3-kinase in severe insulin resistance: a novel variant with impaired insulin-stimulated lipid kinase activity. Diabetologia. 2000 Mar;43(3):321-31. 10768093
  61. Thauvin-Robinet C, Auclair M, Duplomb L, Caron-Debarle M, Avila M, St-Onge J, Le Merrer M, Le Luyer B, Heron D, Mathieu-Dramard M, Bitoun P, Petit JM, Odent S, Amiel J, Picot D, Carmignac V, Thevenon J, Callier P, Laville M, Reznik Y, Fagour C, Nunes ML, Capeau J, Lascols O, Huet F, Faivre L, Vigouroux C, Riviere JB: PIK3R1 mutations cause syndromic insulin resistance with lipoatrophy. Am J Hum Genet. 2013 Jul 11;93(1):141-9. doi: 10.1016/j.ajhg.2013.05.019. Epub 2013 Jun 27. 23810378
  62. Chudasama KK, Winnay J, Johansson S, Claudi T, Konig R, Haldorsen I, Johansson B, Woo JR, Aarskog D, Sagen JV, Kahn CR, Molven A, Njolstad PR: SHORT syndrome with partial lipodystrophy due to impaired phosphatidylinositol 3 kinase signaling. Am J Hum Genet. 2013 Jul 11;93(1):150-7. doi: 10.1016/j.ajhg.2013.05.023. Epub 2013 Jun 27. 23810379