Abstract
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.
Keywords
- Inositol Phosphate
- Oncogene Product
- Inositol Polyphosphates
- Traditional Pathway
- Adrenal Glomerulosa Cell
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
M.J. Berridge and R.F. Irvine, Inositol phosphates and cell signalling, Nature. 341:197–205 (1989).
V.S. Bansal and P.W. Majerus, Phosphatidylinositol-derived precursors and signals, Annu. Rev. Cell Biol. 6:41–67 (1990).
L.C. Cantley, K.R. Auger, C. Carpenter, B. Duckworth, A. Graziani, R. Kapeller, and S. Soltoff, Oncogenes and signal transduction, Cell. 64:281–302 (1991).
B.J. Drucker, H.J. Mamon, and T.M. Roberts, Oncogenes, growth factors and signal transduction, N Eng J Med. 321:1383–91 (1989).
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).
C.A. Koch, D. Anderson, M.F. Moran, C. Ellis, and T. Pawson, SH2 and SH3 domains: Elements that control interactions of cytoplasmic signaling proteins, Science. 252: 668–74. (1991)
I.G. Macara, Oncogenes and cellular signal transduction, Physiol Rev. 69: 797–820. (1989)
Y. Sugimoto, M. Whitman, L.C. Cantley, and R.L. Erikson, Evidence that the Rous sarcoma virus transforming gene product phosphorylates phospatidylinositol and diacyglyccrol, Proc Natl Acad Sci USA. 81:2117–21 (1984).
R.M. Johnson, W.J. Wasilenko, R.R. Mattingly, M.J. Weber, and J.C. Garrison, Fibroblasts transformed with v-src show enhanced formation of an inositol tetrakisphosphate, Science. 246: 121–24 (1989).
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).
M. Whitman, D. Kaplan, T. Roberts, and L. Cantley, Evidence for two distinct phosphatidylinositol kinases in fibroblasts: implications for cellular transformation, Biochem J. 247:165–74 (1987).
M. Whitman, C.P. Downes, T. Keeler, T. Keller, and L. Cantley, Type 1 phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate, Nature. 332: 644–46 (1988).
M. Otsu, I. Hiles, I. Gout, M.J. Fry, F. Ruiz-Larrea, G. Panayotou, A. Thompson, R. Dhand, et. al, Characterization of two 85kD. proteins that associate with receptor tyrosine kinases, middle-T/pp60c-src complexes, and PI3-kinase, Cell. 65:91–104 (1991).
L.R. Stephens, P.T. Hawkins, N. Carter, S.B. Chawala, A.J. Morris, et al, L-myo-inositol 1,4,5,6-tetrakisphosphate is present in both mammalian and avian cells, Biochem J. 249:271–82 (1988).
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).
T. Balla, L. Hunyady, A.J. Baukal, and K.J. Catt, Structures and metabolism of inositol tetrakisphosphates and inositol pentakisphosphates in bovine adrenal glomerulosa cells, J Biol Chem. 264: 9386–90 (1989).
P. Grondin, M. Plantavid, C. Sultan, et.al, Interaction of p60c-src, phospholipase C. inositol-lipid and diacylglycerol with the cytoskeletons of thrombin-stimulated platelets. J Biol Chem. 266: 15705–09 (1991).
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).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1992 Springer Science+Business Media New York
About this chapter
Cite this chapter
Wasilenko, W.J. (1992). Phosphoinositides and Cell Growth. In: Vinik, A.I., Sirman, D.J. (eds) Pancreatic Islet Cell Regeneration and Growth. Advances in Experimental Medicine and Biology, vol 321. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3448-8_16
Download citation
DOI: https://doi.org/10.1007/978-1-4615-3448-8_16
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-6526-6
Online ISBN: 978-1-4615-3448-8
eBook Packages: Springer Book Archive