Growth factor-stimulated phosphorylation cascades: activation of growth factor-stimulated MAP kinase.
Protein phosphorylation is an important mechanism in the response of cells to growth factors by which signals can be conveyed from cell surface receptors to intracellular targets. In addition to stimulation of protein tyrosine phosphorylation, activation of growth factor receptors having protein tyrosine kinase activity leads to dramatic alterations in the levels of protein serine/threonine phosphorylation. Several growth factor-stimulated serine/threonine-specific kinases have been identified as potential mediators of such signalling. MAP (microtubule-associated protein) kinase has emerged as a very interesting member of this group, because it activates a separate kinase, pp90rsk, which is also growth factor-stimulated. MAP kinase itself appears to be regulated by protein phosphorylation, because it can be inactivated by protein phosphatases. We have identified two 60 kDa proteins that promote the phosphorylation and full activation of MAP kinase in a manner paralleling its activation by growth factors in intact cells. These 'MAP kinase activators' are themselves stimulated by growth factors, suggesting that they function as intermediates between the MAP kinase and cell surface receptors in a growth factor-stimulated kinase cascade. Identification of the components of this protein kinase cascade reveals a mechanism by which at least some of the effects of receptor tyrosine kinases can be mediated through serine/threonine phosphorylation.
Ahn
N G
NG
Department of Biochemistry, University of Washington, Seattle 98185.
Seger
R
R
Bratlien
R L
RL
Krebs
E G
EG
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D004789:Enzyme Activation / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology*; D008970:Molecular Weight; D010766:Phosphorylation; D011494:Protein Kinases / Q000187:drug effects*; D011506:Proteins / Q000302:isolation & purification
D006133:Growth Substances; D011506:Proteins; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases