Constitutive Signaling by Aberrant PI3K in Cancer

Urick ME, Rudd ML, Godwin AK, Sgroi D, Merino M, Bell DW. PIK3R1 (p85a) is somatically mutated at high frequency in primary endometrial cancer. Cancer Res. 2011 Jun 15;71(12):4061–7. PMID: 21478295; PMCID: PMC3117071.; Sun M, Hillmann P, Hofmann BT, Hart JR, Vogt PK. Cancer-derived mutations in the regulatory subunit p85alpha of phosphoinositide 3-kinase function through the catalytic subunit p110alpha. Proc Natl Acad Sci U S A. 2010 Aug 31;107(35):15547–52. PMID: 20713702; PMCID: PMC2932613.; Zhao L, Vogt PK. Hot-spot mutations in p110alpha of phosphatidylinositol 3-kinase (pI3K): differential interactions with the regulatory subunit p85 and with RAS. Cell Cycle. 2010 Feb 01;9(3):596–600. PMID: 20009532; PMCID: PMC2835815.; Jaiswal BS, Janakiraman V, Kljavin NM, Chaudhuri S, Stern HM, Wang W, Kan Z, Dbouk HA, Peters BA, Waring P, Dela Vega T, Kenski DM, Bowman KK, Lorenzo M, Li H, Wu J, Modrusan Z, Stinson J, Eby M, Yue P, Kaminker JS, de Sauvage FJ, Backer JM, Seshagiri S. Somatic mutations in p85alpha promote tumorigenesis through class IA PI3K activation. Cancer Cell. 2009 Dec 08;16(6):463–74. PMID: 19962665; PMCID: PMC2804903.; Horn S, Bergholz U, Jücker M, McCubrey JA, Trümper L, Stocking C, Bäsecke J. Mutations in the catalytic subunit of class IA PI3K confer leukemogenic potential to hematopoietic cells. Oncogene. 2008 Jul 03;27(29):4096–106. doi: 10.1038/onc.2008.40. PMID: 18317450.; 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. doi: 10.1126/science.1150799. PMID: 18079394.; 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. doi: 10.1126/science.1135394. PMID: 17626883.; Zhao JJ, Liu Z, Wang L, Shin E, Loda MF, Roberts TM. The oncogenic properties of mutant p110alpha and p110beta phosphatidylinositol 3-kinases in human mammary epithelial cells. Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18443–8. PMID: 16339315; PMCID: PMC1317954.

Metabolites

ATP(4-)

Formula: C10H12N5O13P3 (502.9644492)

CAS ID:

ADP(3-)

Formula: C10H12N5O10P2 (424.0059412)

CAS ID:



Enzyme

EC Number name full name note
2.7.1.137 phosphatidylinositol 3-kinase ATP:1-phosphatidyl-1D-myo-inositol 3-phosphotransferase
2.7.1.153 phosphatidylinositol-4,5-bisphosphate 3-kinase ATP:1-phosphatidyl-1D-myo-inositol-4,5-bisphosphate 3-phosphotransferase
2.7.11.1 non-specific serine/threonine protein kinase ATP:protein phosphotransferase (non-specific)


Proteins

Protein ID name full name