Phosphoinositides and Cell Growth
Phosphoinositides are a class of membrane phospholipids that serve as precursors to the important second messengers inositol(1,4,5)P3 and diacylglycerol, which mediate the release of intracellular calcium and the activation of protein kinase C, respectively.1,2 The key event in the production of these signals is the hydrolysis of phoshatidylinositol(4,5)P2 by phospholipase C. This traditional pathway of signal transduction is utilized by activated receptors for a variety of diverse stimuli, including hormones, growth factors, neurotransmitters and chemotactic factors. Recently, several new pathways of phosphoinositide (PI) metabolism have been discovered in cells stimulated by growth factors or transformed by certain oncogene products.1,3 These new pathways branch off the classical routes of PI hydrolysis and appear to be linked to poorly understood events in cellular regulation that are distinct from calcium release and C-kinase activation. In this discussion, several of these new aspects of PI metabolism relating to cell transformation will be illustrated, and a model for neoplastic transformation by the src tyrosine kinase oncogene, will be presented.
KeywordsInositol Phosphate Oncogene Product Inositol Polyphosphates Traditional Pathway Adrenal Glomerulosa Cell
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- 5.J.T. Parsons and M.J. Weber, Genetics of SrC: structure and functional organization of a protein tyrosine kinase, Curr Top Microbiol Immunol. 147:80–127 (1989).Google Scholar
- 10.R.R. Mattingly, L.R. Stephens, R.F. Irvine, and J.C. Garrison, Effects of transformation with the v-src oncogene on inositol phosphate metabolism in rat-I cells: d-myo-inositol 1,4,5,6-tetrakisphosphate is increased in v-src transformed fibroblasts and can be synthesized from d-myo-inositol 1,3,4-trisphosphate in cytosolic extracts, J Biol Chem. 266:15144–53 (1991).PubMedGoogle Scholar
- 15.F.S. Menniti, K.G. Oliver, K. Nogimori, J.F. Obie, S. Shears, and J.W. Putney Jr., Origins of myo-inositol tetrakisphosphates in agonist-stimulated rat pancreatoma cells. Stimulation by bombesin of myoinositol 1,3,4,5,6-pentakisphosphate to myo-inositol 3,4,5,6-tetrakisphosphate, J Biol Chem. 265: 11167–76 (1990).PubMedGoogle Scholar
- 18.A. Sjolander, K. Yamamoto, B.E. Huber, and E.G. Lapetina, Association of p21ras with phosphatidylinositol 3-kinase, J Biol Chem. 88:7908–12 (1991).Google Scholar