Phosphoinositide 3-kinase: a new effector in signal transduction?
Interest in phosphoinositide 3-kinase (PI 3-kinase) has been fuelled by its identification as a major phosphotyrosyl protein detected in cells following growth factor stimulation and oncogenic transformation. It is found complexed with activated growth factor receptors and non-receptor tyrosine kinases, thus suggesting that it participates in the signal transduction pathways initiated by the activation of tyrosine kinases. PI 3-kinase phosphorylates the 3-position in the inositol ring of the well known inositol phospholipids in vitro giving phosphatidylinositol 3-phosphate, phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate [PtdIns3P, PtdIns(3,4)P2 and PtdIns(3,4,5)P3], respectively. The cellular levels of PtdIns(3,4)P2 and PtdIns(3,4,5)P3 rapidly increase in circumstances where PI 3-kinase becomes complexed with tyrosine kinases. Accumulation of the same lipids also occurs in platelets and neutrophils following stimulation of G-protein linked alpha-thrombin and chemotactic peptide receptors, respectively, leading to speculation that one or both of these lipids is a new second messenger whose function is not yet known. This review brings together recent information on the isolation, characterization and regulation of PI 3-kinase, the cellular occurrence of 3-phosphorylated inositol phospholipids and possible functions of the PI 3-kinase pathway in cell signalling.
Downes
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CP
Department Biochemistry, University of Dundee, U.K.
Carter
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AN
D019870:1-Phosphatidylinositol 4-Kinase; D000818:Animals; D002455:Cell Division; D019204:GTP-Binding Proteins / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000378:metabolism*; D010770:Phosphotransferases / Q000302:isolation & purification / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015290:Second Messenger Systems; D015398:Signal Transduction; D013379:Substrate Specificity
D006133:Growth Substances; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; C060974:phosphatidylinositol 3,4,5-triphosphate; D010770:Phosphotransferases; D019870:1-Phosphatidylinositol 4-Kinase; D011505:Protein-Tyrosine Kinases; D019204:GTP-Binding Proteins