PIK3R2 explained

Phosphatidylinositol 3-kinase regulatory subunit beta is an enzyme that in humans is encoded by the PIK3R2 gene.^{[1] [2]}

A recent study on gene expression indicated that the PIK3R2 gene might have a key role in pan-cancer prognosis.^[3]

Interactions

PIK3R2 has been shown to interact with:

• CRKL^[4]
• Cbl gene,^{[5] [6]}
• Epidermal growth factor,
• FYN,^[7]
• HER2/neu,^[7]
• Macrophage colony-stimulating factor,^[7] and
• PIK3CD.^[8]

Clinical relevance

PIK3R2 mutations were recently shown to be associated with polymicrogyria.^[9]

Further reading

• Lee C, Liu QH, Tomkowicz B, Yi Y, Freedman BD, Collman RG . Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited signaling pathways . Journal of Leukocyte Biology . 74 . 5 . 676–682 . November 2003 . 12960231 . 10.1189/jlb.0503206 . 11362623 . free .
• Gout I, Dhand R, Panayotou G, Fry MJ, Hiles I, Otsu M, Waterfield MD . Expression and characterization of the p85 subunit of the phosphatidylinositol 3-kinase complex and a related p85 beta protein by using the baculovirus expression system . The Biochemical Journal . 288 (Pt 2) . 2 . 395–405 . December 1992 . 1334406 . 1132024 . 10.1042/bj2880395 .
• Carpenter CL, Duckworth BC, Auger KR, Cohen B, Schaffhausen BS, Cantley LC . Purification and characterization of phosphoinositide 3-kinase from rat liver . The Journal of Biological Chemistry . 265 . 32 . 19704–19711 . November 1990 . 2174051 . 10.1016/S0021-9258(17)45429-9 . free .
• Truitt KE, Hicks CM, Imboden JB . Stimulation of CD28 triggers an association between CD28 and phosphatidylinositol 3-kinase in Jurkat T cells . The Journal of Experimental Medicine . 179 . 3 . 1071–1076 . March 1994 . 7509360 . 2191424 . 10.1084/jem.179.3.1071 .
• Herbst R, Shearman MS, Jallal B, Schlessinger J, Ullrich A . Formation of signal transfer complexes between stem cell and platelet-derived growth factor receptors and SH2 domain proteins in vitro . Biochemistry . 34 . 17 . 5971–5979 . May 1995 . 7537096 . 10.1021/bi00017a026 .
• 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 . The Journal of Biological Chemistry . 270 . 26 . 15639–15643 . June 1995 . 7541045 . 10.1074/jbc.270.26.15639 . free .
• He W, O'Neill TJ, Gustafson TA . Distinct modes of interaction of SHC and insulin receptor substrate-1 with the insulin receptor NPEY region via non-SH2 domains . The Journal of Biological Chemistry . 270 . 40 . 23258–23262 . October 1995 . 7559478 . 10.1074/jbc.270.40.23258 . free .
• Kapeller R, Toker A, Cantley LC, Carpenter CL . Phosphoinositide 3-kinase binds constitutively to alpha/beta-tubulin and binds to gamma-tubulin in response to insulin . The Journal of Biological Chemistry . 270 . 43 . 25985–25991 . October 1995 . 7592789 . 10.1074/jbc.270.43.25985 . free .
• Hartley D, Meisner H, Corvera S . Specific association of the beta isoform of the p85 subunit of phosphatidylinositol-3 kinase with the proto-oncogene c-cbl . The Journal of Biological Chemistry . 270 . 31 . 18260–18263 . August 1995 . 7629144 . 10.1074/jbc.270.31.18260 . free .
• Pandey A, Lazar DF, Saltiel AR, Dixit VM . Activation of the Eck receptor protein tyrosine kinase stimulates phosphatidylinositol 3-kinase activity . The Journal of Biological Chemistry . 269 . 48 . 30154–30157 . December 1994 . 7982920 . 10.1016/S0021-9258(18)43790-8 . free .
• August A, Dupont B . CD28 of T lymphocytes associates with phosphatidylinositol 3-kinase . International Immunology . 6 . 5 . 769–774 . May 1994 . 8080844 . 10.1093/intimm/6.5.769 .
• Fukazawa T, Miyake S, Band V, Band H . Tyrosine phosphorylation of Cbl upon epidermal growth factor (EGF) stimulation and its association with EGF receptor and downstream signaling proteins . The Journal of Biological Chemistry . 271 . 24 . 14554–14559 . June 1996 . 8662998 . 10.1074/jbc.271.24.14554 . free .
• Milani D, Mazzoni M, Borgatti P, Zauli G, Cantley L, Capitani S . Extracellular human immunodeficiency virus type-1 Tat protein activates phosphatidylinositol 3-kinase in PC12 neuronal cells . The Journal of Biological Chemistry . 271 . 38 . 22961–22964 . September 1996 . 8798481 . 10.1074/jbc.271.38.22961 . free .
• Sattler M, Salgia R, Shrikhande G, Verma S, Pisick E, Prasad KV, Griffin JD . Steel factor induces tyrosine phosphorylation of CRKL and binding of CRKL to a complex containing c-kit, phosphatidylinositol 3-kinase, and p120(CBL) . The Journal of Biological Chemistry . 272 . 15 . 10248–10253 . April 1997 . 9092574 . 10.1074/jbc.272.15.10248 . free .
• Vanhaesebroeck B, Welham MJ, Kotani K, Stein R, Warne PH, Zvelebil MJ, Higashi K, Volinia S, Downward J, Waterfield MD . 6 . P110delta, a novel phosphoinositide 3-kinase in leukocytes . Proceedings of the National Academy of Sciences of the United States of America . 94 . 9 . 4330–4335 . April 1997 . 9113989 . 20722 . 10.1073/pnas.94.9.4330 . free . 1997PNAS...94.4330V .
• Briand G, Barbeau B, Tremblay M . Binding of HIV-1 to its receptor induces tyrosine phosphorylation of several CD4-associated proteins, including the phosphatidylinositol 3-kinase . Virology . 228 . 2 . 171–179 . February 1997 . 9123823 . 10.1006/viro.1996.8399 . free .
• Braunger J, Schleithoff L, Schulz AS, Kessler H, Lammers R, Ullrich A, Bartram CR, Janssen JW . 6 . Intracellular signaling of the Ufo/Axl receptor tyrosine kinase is mediated mainly by a multi-substrate docking-site . Oncogene . 14 . 22 . 2619–2631 . June 1997 . 9178760 . 10.1038/sj.onc.1201123 . free .
• Shepherd PR, Navé BT, Rincon J, Nolte LA, Bevan AP, Siddle K, Zierath JR, Wallberg-Henriksson H . 6 . Differential regulation of phosphoinositide 3-kinase adapter subunit variants by insulin in human skeletal muscle . The Journal of Biological Chemistry . 272 . 30 . 19000–19007 . July 1997 . 9228082 . 10.1074/jbc.272.30.19000 . free .
• Mazerolles F, Barbat C, Fischer A . Down-regulation of LFA-1-mediated T cell adhesion induced by the HIV envelope glycoprotein gp160 requires phosphatidylinositol-3-kinase activity . European Journal of Immunology . 27 . 9 . 2457–2465 . September 1997 . 9341793 . 10.1002/eji.1830270946 . 33397908 .

Notes and References

1. Volinia S, Patracchini P, Otsu M, Hiles I, Gout I, Calzolari E, Bernardi F, Rooke L, Waterfield MD . 6 . Chromosomal localization of human p85 alpha, a subunit of phosphatidylinositol 3-kinase, and its homologue p85 beta . Oncogene . 7 . 4 . 789–793 . April 1992 . 1314371 .
2. Web site: Entrez Gene: PIK3R2 phosphoinositide-3-kinase, regulatory subunit 2 (p85 beta).
3. Chicco D, Alameer A, Rahmati S, Jurman G . Towards a potential pan-cancer prognostic signature for gene expression based on probesets and ensemble machine learning . BioData Mining . 15 . 1 . 28 . November 2022 . 36329531 . 9632055 . 10.1186/s13040-022-00312-y . 1756-0381 . free .
4. Sattler M, Salgia R, Shrikhande G, Verma S, Pisick E, Prasad KV, Griffin JD . Steel factor induces tyrosine phosphorylation of CRKL and binding of CRKL to a complex containing c-kit, phosphatidylinositol 3-kinase, and p120(CBL) . The Journal of Biological Chemistry . 272 . 15 . 10248–10253 . April 1997 . 9092574 . 10.1074/jbc.272.15.10248 . free .
5. Lin H, Martelli MP, Bierer BE . The involvement of the proto-oncogene p120 c-Cbl and ZAP-70 in CD2-mediated T cell activation . International Immunology . 13 . 1 . 13–22 . January 2001 . 11133830 . 10.1093/intimm/13.1.13 . free .
6. Hartley D, Meisner H, Corvera S . Specific association of the beta isoform of the p85 subunit of phosphatidylinositol-3 kinase with the proto-oncogene c-cbl . The Journal of Biological Chemistry . 270 . 31 . 18260–18263 . August 1995 . 7629144 . 10.1074/jbc.270.31.18260 . free .
7. Gout I, Dhand R, Panayotou G, Fry MJ, Hiles I, Otsu M, Waterfield MD . Expression and characterization of the p85 subunit of the phosphatidylinositol 3-kinase complex and a related p85 beta protein by using the baculovirus expression system . The Biochemical Journal . 288 (Pt 2) . 2 . 395–405 . December 1992 . 1334406 . 1132024 . 10.1042/bj2880395 .
8. Vanhaesebroeck B, Welham MJ, Kotani K, Stein R, Warne PH, Zvelebil MJ, Higashi K, Volinia S, Downward J, Waterfield MD . 6 . P110delta, a novel phosphoinositide 3-kinase in leukocytes . Proceedings of the National Academy of Sciences of the United States of America . 94 . 9 . 4330–4335 . April 1997 . 9113989 . 20722 . 10.1073/pnas.94.9.4330 . free . 1997PNAS...94.4330V .
9. Mirzaa GM, Conti V, Timms AE, Smyser CD, Ahmed S, Carter M, Barnett S, Hufnagel RB, Goldstein A, Narumi-Kishimoto Y, Olds C, Collins S, Johnston K, Deleuze JF, Nitschké P, Friend K, Harris C, Goetsch A, Martin B, Boyle EA, Parrini E, Mei D, Tattini L, Slavotinek A, Blair E, Barnett C, Shendure J, Chelly J, Dobyns WB, Guerrini R . 6 . Characterisation of mutations of the phosphoinositide-3-kinase regulatory subunit, PIK3R2, in perisylvian polymicrogyria: a next-generation sequencing study . The Lancet. Neurology . 14 . 12 . 1182–1195 . December 2015 . 26520804 . 4672724 . 10.1016/S1474-4422(15)00278-1 .