Phosphatidylinositol 3-kinase regulatory subunit alpha is an
enzyme that in humans is encoded by the PIK3R1gene.[5]
Function
Phosphatidylinositol 3-kinase phosphorylates the
inositol ring of
phosphatidylinositol at the 3-prime position. The enzyme comprises a 110 kD catalytic subunit and a regulatory subunit of either 85, 55, or 50 kD. The Pik3r1 gene locus encodes the 85 kD regulatory subunit, as well as 55 and 50 kD regulatory subunits. It used to be thought that alternative splicing of this gene resulted in three transcript variants encoding different isoforms.[6] In fact, it has since been shown that the 55 and 50kD subunits have their own promotors within the gene locus Pik3r1.[7]
Phosphatidylinositol 3-kinase plays an important role in the metabolic actions of
insulin, and a mutation in this gene has been associated with
insulin resistance.[8] Suppression specifically of the 85kD subunit in early murine embryoid body development results in a transient cell-cell adhesion deficiency, mediated by transient downregulation of the adhesion molecule integrin-beta1 (ITGB1).[7]
Clinical significance
Mutations in PIK3R1 are implicated in cases of
breast cancer.[9]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Volinia S, Patracchini P, Otsu M, Hiles I, Gout I, Calzolari E, Bernardi F, Rooke L, Waterfield MD (May 1992). "Chromosomal localization of human p85 alpha, a subunit of phosphatidylinositol 3-kinase, and its homologue p85 beta". Oncogene. 7 (4): 789–93.
PMID1314371.
^
abGurney SM, Forster P, Just U, Schwanbeck R (2011). "Suppression of the PI3K Subunit p85alpha Delays Embryoid Body Development and Inhibits Cell Adhesion". J. Cell. Biochem. 112 (12): 3573–81.
doi:
10.1002/jcb.23285.
PMID11313349.
S2CID206020214.
^Zhang S, Broxmeyer HE (1999). "p85 subunit of PI3 kinase does not bind to human Flt3 receptor, but associates with SHP2, SHIP, and a tyrosine-phosphorylated 100-kDa protein in Flt3 ligand-stimulated hematopoietic cells". Biochem. Biophys. Res. Commun. 254 (2): 440–5.
doi:
10.1006/bbrc.1998.9959.
PMID9918857.
^Dufour C, Guenou H, Kaabeche K, Bouvard D, Sanjay A, Marie PJ (2008). "FGFR2-Cbl interaction in lipid rafts triggers attenuation of PI3K/Akt signaling and osteoblast survival". Bone. 42 (6): 1032–9.
doi:
10.1016/j.bone.2008.02.009.
PMID18374639.
^Lin J, Adam RM, Santiestevan E, Freeman MR (1999). "The phosphatidylinositol 3'-kinase pathway is a dominant growth factor-activated cell survival pathway in LNCaP human prostate carcinoma cells". Cancer Res. 59 (12): 2891–7.
PMID10383151.
^Crouin C, Arnaud M, Gesbert F, Camonis J, Bertoglio J (2001). "A yeast two-hybrid study of human p97/Gab2 interactions with its SH2 domain-containing binding partners". FEBS Lett. 495 (3): 148–53.
doi:
10.1016/S0014-5793(01)02373-0.
PMID11334882.
S2CID24499468.
^Fuhrer DK, Yang YC (1996). "Complex formation of JAK2 with PP2A, P13K, and Yes in response to the hematopoietic cytokine interleukin-11". Biochem. Biophys. Res. Commun. 224 (2): 289–96.
doi:
10.1006/bbrc.1996.1023.
PMID8702385.
^Lan Z, Wu H, Li W, Wu S, Lu L, Xu M, Dai W (2000). "Transforming activity of receptor tyrosine kinase tyro3 is mediated, at least in part, by the PI3 kinase-signaling pathway". Blood. 95 (2): 633–8.
doi:
10.1182/blood.V95.2.633.
PMID10627473.
Benito M, Valverde AM, Lorenzo M (1996). "IGF-I: a mitogen also involved in differentiation processes in mammalian cells". Int. J. Biochem. Cell Biol. 28 (5): 499–510.
doi:
10.1016/1357-2725(95)00168-9.
PMID8697095.
Snapper SB, Rosen FS (1999). "The Wiskott-Aldrich syndrome protein (WASP): roles in signaling and cytoskeletal organization". Annu. Rev. Immunol. 17: 905–29.
doi:
10.1146/annurev.immunol.17.1.905.
PMID10358777.
Katada T, Kurosu H, Okada T, Suzuki T, Tsujimoto N, Takasuga S, Kontani K, Hazeki O, Ui M (1999). "Synergistic activation of a family of phosphoinositide 3-kinase via G-protein coupled and tyrosine kinase-related receptors". Chem. Phys. Lipids. 98 (1–2): 79–86.
doi:
10.1016/S0009-3084(99)00020-1.
PMID10358930.
Greenway AL, Holloway G, McPhee DA, Ellis P, Cornall A, Lidman M (2003). "HIV-1 Nef control of cell signalling molecules: multiple strategies to promote virus replication". J. Biosci. 28 (3): 323–35.
doi:
10.1007/BF02970151.
PMID12734410.
S2CID33749514.
Leavitt SA, SchOn A, Klein JC, Manjappara U, Chaiken IM, Freire E (2004). "Interactions of HIV-1 proteins gp120 and Nef with cellular partners define a novel allosteric paradigm". Curr. Protein Pept. Sci. 5 (1): 1–8.
doi:
10.2174/1389203043486955.
PMID14965316.
Joseph AM, Kumar M, Mitra D (2005). "Nef: "necessary and enforcing factor" in HIV infection". Curr. HIV Res. 3 (1): 87–94.
doi:
10.2174/1570162052773013.
PMID15638726.
1bfi: SOLUTION STRUCTURE OF THE C-TERMINAL SH2 DOMAIN OF THE P85ALPHA REGULATORY SUBUNIT OF PHOSPHOINOSITIDE 3-KINASE, NMR, 30 STRUCTURES
1bfj: SOLUTION STRUCTURE OF THE C-TERMINAL SH2 DOMAIN OF THE P85ALPHA REGULATORY SUBUNIT OF PHOSPHOINOSITIDE 3-KINASE, NMR, MINIMIZED AVERAGE STRUCTURE
1fu5: NMR STRUCTURE OF THE N-SH2 DOMAIN OF THE P85 SUBUNIT OF PI3-KINASE COMPLEXED TO A DOUBLY PHOSPHORYLATED PEPTIDE DERIVED FROM POLYOMAVIRUS MIDDLE T ANTIGEN
1fu6: NMR STRUCTURE OF THE N-SH2 DOMAIN OF THE P85 SUBUNIT OF PI3-KINASE
1h9o: PHOSPHATIDYLINOSITOL 3-KINASE, P85-ALPHA SUBUNIT: C-TERMINAL SH2 DOMAIN COMPLEXED WITH A TYR751 PHOSPHOPEPTIDE FROM THE PDGF RECEPTOR, CRYSTAL STRUCTURE AT 1.79 A
1oo3: P395S mutant of the p85 regulatory subunit of the N-terminal src homology 2 domain of PI3-Kinase
1oo4: P395S mutant of the p85 regulatory subunit of the N-terminal src homology 2 domain of PI3-Kinase complexed to a peptide derived from PDGFr
1pic: PHOSPHATIDYLINOSITOL 3-KINASE, P85-ALPHA SUBUNIT: C-TERMINAL SH2 DOMAIN COMPLEXED WITH A TYR751 PHOSPHOPEPTIDE FROM THE PDGF RECEPTOR, NMR, MINIMIZED MEAN STRUCTURE
1pks: STRUCTURE OF THE PI3K SH3 DOMAIN AND ANALYSIS OF THE SH3 FAMILY
1pkt: STRUCTURE OF THE PI3K SH3 DOMAIN AND ANALYSIS OF THE SH3 FAMILY
1pnj: SOLUTION STRUCTURE AND LIGAND-BINDING SITE OF THE SH3 DOMAIN OF THE P85ALPHA SUBUNIT OF PHOSPHATIDYLINOSITOL 3-KINASE
1qad: Crystal Structure of the C-Terminal SH2 Domain of the P85 alpha Regulatory Subunit of Phosphoinositide 3-Kinase: An SH2 domain mimicking its own substrate
2iug: CRYSTAL STRUCTURE OF THE PI3-KINASE P85 N-TERMINAL SH2 DOMAIN
2iuh: CRYSTAL STRUCTURE OF THE PI3-KINASE P85 N-TERMINAL SH2 DOMAIN IN COMPLEX WITH C-KIT PHOSPHOTYROSYL PEPTIDE
2iui: CRYSTAL STRUCTURE OF THE PI3-KINASE P85 N-TERMINAL SH2 DOMAIN IN COMPLEX WITH PDGFR PHOSPHOTYROSYL PEPTIDE
2pna: STRUCTURE OF AN SH2 DOMAIN OF THE P85 ALPHA SUBUNIT OF PHOSPHATIDYLINOSITOL-3-OH KINASE
2pnb: STRUCTURE OF AN SH2 DOMAIN OF THE P85 ALPHA SUBUNIT OF PHOSPHATIDYLINOSITOL-3-OH KINASE
2pni: SOLUTION STRUCTURE AND LIGAND-BINDING SITE OF THE SH3 DOMAIN OF THE P85ALPHA SUBUNIT OF PHOSPHATIDYLINOSITOL 3-KINASE