Protein phosphorylation and growth control.
Many growth factor receptors and retroviral transforming proteins share the property of phosphorylating proteins on tyrosine. Several substrates for both types of protein-tyrosine kinase have been identified. Treatment of quiescent cells with growth factors such as EGF and PDGF, whose receptors have ligand-stimulated protein-tyrosine kinase activities, induces tyrosine phosphorylation of three proteins, p45, p42 and p41. Two phosphorylated forms of p42 are found, the more basic of which is present in some but not all cells transformed by viral protein-tyrosine kinases. p42 is rapidly (as early as 1 min) but transiently (decreased to baseline by 2h) phosphorylated following PGDF or EGF treatment of quiescent fibroblasts. At saturating levels of mitogen the stoichiometry of p42 phosphorylation is greater than 50%. p42 is a highly conserved, rare (0.002% of total cell protein), soluble cytoplasmic protein. IGF I and insulin, whose receptors also have ligand-stimulated protein-tyrosine kinase activity, induce p42 phosphorylation in appropriate cells. In the case of insulin this effect has been observed in cells with large numbers of insulin receptors. p42 is also phosphorylated in response to mitogens whose receptors lack protein-tyrosine kinase activity, for example 12-O-tetradecanoylphorbol-13-acetate (TPA) and thrombin. For TPA there is evidence that this is an indirect effect due to the activation of a protein-serine/threonine kinase. On the basis of the highly conserved nature of this response and its generality, it seems likely that tyrosine phosphorylation of p42 is important for at least early responses to mitogens.
D000818:Animals; D002472:Cell Transformation, Viral; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008934:Mitogens / Q000494:pharmacology; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D011956:Receptors, Cell Surface / Q000032:analysis; D017479:Receptors, Platelet-Derived Growth Factor; D017451:Receptors, Somatomedin; D012190:Retroviridae / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D006133:Growth Substances; D008934:Mitogens; D009856:Oncogene Proteins, Viral; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D014443:Tyrosine; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D066246:ErbB Receptors; D017479:Receptors, Platelet-Derived Growth Factor; D011493:Protein Kinase C