phosphoinositide-3-kinase (phosphatidylinositol-3-kinase, PI3K)
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Function
- phosphorylates PIP2 to PIP3
- allegedly phosphorylates protein subtrates as well
- p110 catalytic subunit of PI 3-kinase is active only when bound through its N-terminal region to the p85 subunit[3]
- role in cellular responses to growth factors including:[4]
- mitogenesis
- insulin stimulation of glucose transport
- membrane trafficking
- activated by multiple tyrosine kinase receptors including:
- required for PDGF signalling
- appears to be required for NGF-mediated survival of PC-12 cells[4]
- stimulates ras-dependent cellular processes including differentiation of PC-12 cells
- role of PI 3-kinase in NGF-mediated PC-12 cell survival is distinct from ras-mediated differentiation[4]
- PI 3-kinase & p21ras may form a complex
- associates with the focal adhesion kinase (FAK) & src & the cytoskeletal protein alpha-actinin (integrin dependent)[5]
- activated in vitro by Rho
PI3K PIP2 + ATP ---> PIP3 + ADP
* see figure
Pharmacology
- copanlisib (Aliqopa) FDA-approved for refractory follicular lymphoma inhibits PI3K[6]
More general terms
References
- ↑ Nolan RD, Lapetina EG. Thrombin stimulates the production of a novel polyphosphoinositide in human platelets. J Biol Chem. 1990 Feb 15;265(5):2441-5. PMID: https://www.ncbi.nlm.nih.gov/pubmed/2154447
- ↑ Cantley LC, Auger KR, Carpenter C, Duckworth B, Graziani A, Kapeller R, Soltoff S. Oncogenes and signal transduction. Cell. 1991 Jan 25;64(2):281-302. Review. Erratum in: Cell 1991 May 31;65(5):following 914. PMID: https://www.ncbi.nlm.nih.gov/pubmed/1846320
- ↑ 3.0 3.1 Hu Q, Klippel A, Muslin AJ, Fantl WJ, Williams LT. Ras-dependent induction of cellular responses by constitutively active phosphatidylinositol-3 kinase. Science. 1995 Apr 7;268(5207):100-2. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7701328
- ↑ 4.0 4.1 4.2 4.3 Yao R, Cooper GM. Requirement for phosphatidylinositol-3 kinase in the prevention of apoptosis by nerve growth factor. Science. 1995 Mar 31;267(5206):2003-6. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7701324
- ↑ 5.0 5.1 Clark EA & Brugge JS Integrins and signal transduction pathways: the road taken. Science 268:233 1995 PMID: https://www.ncbi.nlm.nih.gov/pubmed/7716514
- ↑ 6.0 6.1 Gever J, MedPage Today. September 14, 2017 Novel Kinase Inhibitor OK'd for Follicular Lymphoma. Copanlisib (Aliqopa) approved as third-line therapy. https://www.medpagetoday.com/HematologyOncology/Lymphoma/67913