Requirement for integration of signals from two distinct phosphorylation pathways for activation of MAP kinase.
MAP kinase (relative molecular mass, 42,000), a low abundance serine--threonine protein kinase, is transiently activated in many cell types by a variety of mitogens, including insulin, epidermal growth factor, and phorbol esters. In vitro, MAP kinase will phosphorylate and reactivate S6 kinase II previously inactivated by phosphatase treatment. Because many of the stimuli that activate MAP kinase are also stimulators of cell proliferation, and regulation of the cell cycle seems to involve a network of protein kinases, MAP kinase could be important in the transmission of stimuli eventually leading to the progression from G0 to G1 in the cell cycle. Activated MAP kinase contains both phosphotyrosine and phosphothreonine. We report here that MAP kinase can be deactivated completely by treatment with either phosphatase 2A, a protein phosphatase specific for phosphoserine and phosphothreonine, or CD45, a phosphotyrosine-specific protein phosphatase. We demonstrate that MAP kinase is only active when both tyrosyl and threonyl residues are phosphorylated and suggest therefore that the enzyme functions in vivo to integrate signals from two distinct transduction pathways.
Anderson
N G
NG
Department of Internal Medicine and Pharmacology, University of Virginia School of Medicine, Charlottesville 22908.
Maller
J L
JL
Tonks
N K
NK
Sturgill
T W
TW
D000255:Adenosine Triphosphate / Q000378:metabolism; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D000943:Antigens, Differentiation; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002478:Cells, Cultured; D004789:Enzyme Activation; D006649:Histocompatibility Antigens; D007700:Kinetics; D017493:Leukocyte Common Antigens; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors; D051379:Mice; D008970:Molecular Weight; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D054648:Protein Phosphatase 2; D012969:Sodium Fluoride / Q000494:pharmacology; D013379:Substrate Specificity
D000596:Amino Acids; D000943:Antigens, Differentiation; D006649:Histocompatibility Antigens; D008562:Membrane Glycoproteins; D010761:Phosphorus Radioisotopes; D000255:Adenosine Triphosphate; D012969:Sodium Fluoride; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D017493:Leukocyte Common Antigens