Receptor tyrosine kinase substrates: src homology domains and signal transduction.
Among the intracellular milieu of proteins are molecules with defined biochemical functions that serve as substrates for ligand-activated tyrosine kinase receptors. It seems likely that some of these substrate molecules are elements of a critical signaling pathway used by growth factors to control cell proliferation and subverted by oncogenes to deregulate this process. Although the process of cell growth and division is relatively slow compared with other hormonally regulated responses, homeostasis in a human being requires approximately 20 x 10(6) cell divisions per second for the renewal of various cell populations. This review summarizes the present understanding of tyrosine kinase substrates that seem likely to have key roles in the signal transduction pathway that regulates cell proliferation. This includes structural features of these molecules, the influence of tyrosine phosphorylation on their functions, the biological roles of these proteins, and the capacity of these substrates to associate with activated receptor tyrosine kinases.
Carpenter
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Department of Biochemistry and Medicine (Dermatology), Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146.
D000818:Animals; D066246:ErbB Receptors / Q000502:physiology; D020690:GTPase-Activating Proteins; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins / Q000737:chemistry*; D010770:Phosphotransferases / Q000737:chemistry / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011506:Proteins / Q000737:chemistry / Q000502:physiology; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000737:chemistry; D011956:Receptors, Cell Surface / Q000502:physiology*; D017479:Receptors, Platelet-Derived Growth Factor / Q000502:physiology; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D010738:Type C Phospholipases / Q000737:chemistry / Q000502:physiology
D020690:GTPase-Activating Proteins; D010750:Phosphoproteins; D011506:Proteins; D011956:Receptors, Cell Surface; D010770:Phosphotransferases; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor; D016392:Proto-Oncogene Proteins pp60(c-src); D010738:Type C Phospholipases