Growth Factors and Polyphosphoinositide Metabolism
The progression of normal cells through the cell cycle is controlled by specific growth factors. Appropriate combinations of these factors at specific times in the G1 phase of the cell cycle are sufficient to commit a cell to a round of DNA synthesis. In attempting to understand how growth factors regulate cell proliferation, we encounter two distinct problems. There is a spatial problem in that the specific receptors that recognise growth factors are in the plasma membrane while the ultimate target of their actions, DNA, is in the nucleus. The second problem, a temporal one, is to understand how the rapid responses that are most readily associated with receptor activation by growth factors are related to the initiation of DNA synthesis that may occur many hours later. One approach to these problems has been to identify the earliest nuclear events that are commonly and perhaps universally associated with growth factor stimulation, and to attempt to relate expression of these specific genes (c-fos and c-myc, for example) both to the early signals generated after receptor activation and to the proteins that control DNA replication (Bravo, this volume; Treisman 1987). However, despite recent progress, the sequence of signals that links the initial interactions between growth factors and their receptors at the plasma membrane with the synthesis of DNA in the nucleus have not yet been identified.
KeywordsEpidermal Growth Factor Receptor Tyrosine Kinase Activity Pertussis Toxin Inositol Phosphate Phosphoinositide Hydrolysis
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