Precisely ordered phosphorylation reactions in the p38 mitogen-activated protein (MAP) kinase cascade

Abstract

Background: MAPK cascades are signaling modules that function as switch generators. Results: In vitro phosphorylation in the p38 MAPK cascade tracked by LC-MS/MS revealed specific phosphorylation intermediates at each level. Conclusion: The p38 MAPK cascade reactions occur through intermediates MEK6/ST* and p38α/TY*. Significance: The precise order of reactions may contribute to the diverse kinetic outputs of the cascades, including those with large Hill coefficients. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.