Pull TAB1 to Activate

Abstract

Members of the mitogen-activated protein kinase (MAPK) family control a wide range of cellular processes and are regulated as part of a cascade of protein kinases that are activated by sequential phosphorylation. Thus, MAPK kinases phosphorylate MAPKs on specific threonine and tyrosine residues, which leads to activation of the MAPK. Ge et al. (see the Perspective by Johnson) now show that there is another way to activate the so-called stress-activated MAPK known as p38α. They isolated proteins that interacted in a yeast system with human p38α and found TAB1 [transforming growth factor β-activated protein kinase 1 (TAK1)-binding protein 1], a protein previously implicated in activating a different protein kinase, TAK1. TAB1 directly interacted with p38α and thereby enhanced autophosphorylation and activation of the p38α enzyme. Studies of signaling to p38α in cultured cells indicated that some stimuli activate p38α by the conventional kinase cascade, whereas others require the interaction with TAB1 and activation of p38α autophosphorylation. B. Ge, H. Gram, F. Di Padova, B. Huang, L. New, R. J. Ulevitch, Y. Luo, J. Han, MAPKK-independent activation of p38α mediated by TAB1-dependent autophosphorylation of p38α. Science 295 , 1291-1294 (2002). [Abstract] [Full Text] G. Johnson, Scaffolding proteins--more than meets the eye. Science 295 , 1249-1250 (2002). [Full Text]