The role of lipid-derived second messengers in cell growth and transformation.
Recent information on the structure of growth factor receptors and oncogenes has advanced our understanding of the biochemical mechanism of growth control. Several peptide growth factor receptors have now been purified and, with a few notable exceptions, they fall into a family of homologous proteins with growth factor-stimulated protein-tyrosine kinase (PTK) activity. Mutations in the genes encoding for both the growth factors and the growth factor receptors of this family have been shown to cause cell transformation. Thus, PTKs have been implicated both in normal growth control and in cell transformation. The critical targets for these PTKs have not been determined. Several but not all growth factors stimulate production of the phosphatidylinositol (PI)-derived second messengers, diacylglycerol and inositol-1,4,5-trisphosphate. By purifying and characterizing the enzymes involved in PI turnover we are attempting to determine how this system is regulated by growth factors and oncogene products. We have found that fibroblasts contain two distinct PI kinases, and that one of these enzymes can be precipitated with antibodies against phosphotyrosine only after addition of platelet-derived growth factor. The relevance of the PI turnover pathway in propagation of growth signals is discussed.
Cantley
L
L
Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111.
Fleischman
L
L
Whitman
M
M
D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D019204:GTP-Binding Proteins / Q000502:physiology; D006133:Growth Substances / Q000494:pharmacology; D008055:Lipids / Q000502:physiology*; D009857:Oncogenes; D010716:Phosphatidylinositols / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology
D006133:Growth Substances; D008055:Lipids; D010716:Phosphatidylinositols; D011493:Protein Kinase C; D019204:GTP-Binding Proteins