Phosphoinositide 3-kinase is activated by phosphopeptides that bind to the SH2 domains of the 85-kDa subunit - PubMed (original) (raw)
. 1993 May 5;268(13):9478-83.
Affiliations
- PMID: 7683653
Free article
Phosphoinositide 3-kinase is activated by phosphopeptides that bind to the SH2 domains of the 85-kDa subunit
C L Carpenter et al. J Biol Chem. 1993.
Free article
Abstract
Tyrosine-phosphorylated peptides based on the regions of polyoma virus middle t antigen and the platelet-derived growth factor receptor that bind phosphoinositide 3-kinase are shown to activate this enzyme 2-3-fold in vitro. The concentrations of the peptides required to activate the enzyme are at least 10-1000-fold higher than the dissociation constants of these peptides for the individual SH2 domains of the 85-kDa subunit (KD < 100 nM). Doubly phosphorylated peptides are more effective than singly phosphorylated peptides. The results suggest that a fraction of the cellular phosphoinositide 3-kinase has SH2 domains with relatively low affinity for phosphopeptides and that binding of phosphopeptides to these enzymes causes activation. Thus, SH2 domains may be involved not only in recruiting the enzyme but also in regulating activity.
Similar articles
- Potent activation of phosphatidylinositol 3'-kinase by simple phosphotyrosine peptides derived from insulin receptor substrate 1 containing two YMXM motifs for binding SH2 domains.
Herbst JJ, Andrews G, Contillo L, Lamphere L, Gardner J, Lienhard GE, Gibbs EM. Herbst JJ, et al. Biochemistry. 1994 Aug 16;33(32):9376-81. doi: 10.1021/bi00198a002. Biochemistry. 1994. PMID: 7520748 - SH2 domains exhibit high-affinity binding to tyrosine-phosphorylated peptides yet also exhibit rapid dissociation and exchange.
Felder S, Zhou M, Hu P, Ureña J, Ullrich A, Chaudhuri M, White M, Shoelson SE, Schlessinger J. Felder S, et al. Mol Cell Biol. 1993 Mar;13(3):1449-55. doi: 10.1128/mcb.13.3.1449-1455.1993. Mol Cell Biol. 1993. PMID: 7680095 Free PMC article. - IRS-1 activates phosphatidylinositol 3'-kinase by associating with src homology 2 domains of p85.
Myers MG Jr, Backer JM, Sun XJ, Shoelson S, Hu P, Schlessinger J, Yoakim M, Schaffhausen B, White MF. Myers MG Jr, et al. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10350-4. doi: 10.1073/pnas.89.21.10350. Proc Natl Acad Sci U S A. 1992. PMID: 1332046 Free PMC article. - Specificity in recognition of phosphopeptides by src-homology 2 domains.
Cantley LC, Songyang Z. Cantley LC, et al. J Cell Sci Suppl. 1994;18:121-6. doi: 10.1242/jcs.1994.supplement_18.18. J Cell Sci Suppl. 1994. PMID: 7533766 - Specific phosphopeptide binding regulates a conformational change in the PI 3-kinase SH2 domain associated with enzyme activation.
Shoelson SE, Sivaraja M, Williams KP, Hu P, Schlessinger J, Weiss MA. Shoelson SE, et al. EMBO J. 1993 Feb;12(2):795-802. doi: 10.1002/j.1460-2075.1993.tb05714.x. EMBO J. 1993. PMID: 8382612 Free PMC article.
Cited by
- Dynamic steps in receptor tyrosine kinase mediated activation of class IA phosphoinositide 3-kinases (PI3K) captured by H/D exchange (HDX-MS).
Burke JE, Williams RL. Burke JE, et al. Adv Biol Regul. 2013 Jan;53(1):97-110. doi: 10.1016/j.jbior.2012.09.005. Epub 2012 Sep 13. Adv Biol Regul. 2013. PMID: 23194976 Free PMC article. - Regulation of lipid binding underlies the activation mechanism of class IA PI3-kinases.
Hon WC, Berndt A, Williams RL. Hon WC, et al. Oncogene. 2012 Aug 9;31(32):3655-66. doi: 10.1038/onc.2011.532. Epub 2011 Nov 28. Oncogene. 2012. PMID: 22120714 Free PMC article. - Role of PI3K/Akt/mTOR pathway in mediating endocrine resistance: concept to clinic.
Skolariki A, D'Costa J, Little M, Lord S. Skolariki A, et al. Explor Target Antitumor Ther. 2022;3(2):172-199. doi: 10.37349/etat.2022.00078. Epub 2022 Apr 24. Explor Target Antitumor Ther. 2022. PMID: 36046843 Free PMC article. Review. - Insulin resistance and diabetes caused by genetic or diet-induced KBTBD2 deficiency in mice.
Zhang Z, Turer E, Li X, Zhan X, Choi M, Tang M, Press A, Smith SR, Divoux A, Moresco EM, Beutler B. Zhang Z, et al. Proc Natl Acad Sci U S A. 2016 Oct 18;113(42):E6418-E6426. doi: 10.1073/pnas.1614467113. Epub 2016 Oct 5. Proc Natl Acad Sci U S A. 2016. PMID: 27708159 Free PMC article. - The Key Role of Calmodulin in KRAS-Driven Adenocarcinomas.
Nussinov R, Muratcioglu S, Tsai CJ, Jang H, Gursoy A, Keskin O. Nussinov R, et al. Mol Cancer Res. 2015 Sep;13(9):1265-73. doi: 10.1158/1541-7786.MCR-15-0165. Epub 2015 Jun 17. Mol Cancer Res. 2015. PMID: 26085527 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
- GM 36624/GM/NIGMS NIH HHS/United States
- CA 34722/CA/NCI NIH HHS/United States
- R01 GM041890/GM/NIGMS NIH HHS/United States
- R01 CA034722/CA/NCI NIH HHS/United States
- GM 41890/GM/NIGMS NIH HHS/United States
LinkOut - more resources
Full Text Sources
Other Literature Sources