PIK3s
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Definition: Phosphoinositide 3-kinases (PI 3-kinases or PI3Ks) are a family of related enzymes that are capable of phosphorylating the 3 position hydroxyl group of the inositol ring of phosphatidylinositol (PtdIns). They are also known as phosphatidylinositol-3-kinases (PI3Ks or PIK3s).
Members of the PIK (phosphatidylinositol kinase)-related kinase family (PIKs) are high molecular weight kinases involved in cell cycle progression, DNA recombination, and the detection of DNA damage
Phosphoinositide 3-kinases (PI3Ks) generate specific inositol lipids implicated in the regulation of cell growth, proliferation, survival, differentiation, and cytoskeletal changes.
Receptor-regulated class I phosphoinositide 3-kinases (PI3Ks) phosphorylate the membrane lipid phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) to PtdIns(3,4,5)P3, which in turn recruits and activates cytosolic effectors involved in proliferation, survival, or chemotaxis.
Subunits
| PIK3CA | PIK3CB | PIK3CD | PIK3CG | |
| PIK3R1 | PIK3R2 | PIK3R3 | PIK3R4 | PIK3R5 |
Function
One of the best characterized targets of PI3K lipids are the protein kinases B (PKBs) or AKTs (AKT1 and AKT2).
AKT2 (MIM.164731) is the isoform of AKT 1 and is enriched in insulin-responsive tissues and has been implicated in the metabolic actions of the hormone.
In quiescent cells, AKT1 resides in the cytosol in a low-activity conformation. Upon cellular stimulation, AKT1 is activated through recruitment to cellular membranes by PI3K lipids and by phosphorylation by 3-prime phosphoinositide-dependent kinase-1 (PDPK1) (MIM.605213).
PTEN
PTEN suppresses phosphoinositol-3-kinase (PI3K) signaling, thereby down-regulating downstream mediators, including the oncogenic serine-threonine kinase AKT1, which in turn regulates the mTOR (mammalian target of rapamycin) growth pathway.
PI3Ks and leukocyte motility
Morphologic polarity is necessary for the motility of mammalian cells. In leukocytes responding to a chemoattractant, this polarity is regulated by activities of small Rho guanosine triphosphatases (Rho GTPases) and the phosphoinositide 3-kinases (PI3Ks). In neutrophils, lipid products of PI3Ks appear to regulate activation of Rho GTPases, are required for cell motility and accumulate asymmetrically to the plasma membrane at the leading edge of polarized cells.
By spatially regulating Rho GTPases and organizing the leading edge of the cell, PI3Ks and their lipid products could play pivotal roles not only in establishing leukocyte polarity but also as compass molecules that tell the cell where to crawl.
See also
References
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Fingar DC, Blenis J. Target of rapamycin (TOR): an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression. Oncogene. 2004 Apr 19;23(18):3151-71. PMID: 15094765
Weaver SA, Ward SG. Phosphoinositide 3-kinases in the gut: a link between inflammation and cancer? Trends Mol Med. 2001 Oct;7(10):455-62. PMID: 11597520
Rickert P, Weiner OD, Wang F, Bourne HR, Servant G. Leukocytes navigate by compass: roles of PI3Kgamma and its lipid products. Trends Cell Biol. 2000 Nov;10(11):466-73. PMID: 11050418