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J Cell Physiol

Title:		p115 Rho GTPase activating protein interacts with MEKK1
Author(s):		Christerson LB; Gallagher E; Vanderbilt CA; Whitehurst AW; Wells C; Kazempour R; Sternweis PC; Cobb MH;
Address:		"Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9041, USA"
Journal Title:		J Cell Physiol
Year:		2002
Volume:		192
Issue:		2
Page Number:		200 - 208
DOI:		10.1002/jcp.10125
ISSN/ISBN:		0021-9541 (Print) 0021-9541 (Linking)
Abstract:		"Mammalian MAP/ERK kinase kinase 1 (MEKK1) was identified as a mammalian homolog of Ste11p of the yeast pheromone-induced mating pathway. Like Ste11p, MEKK1 is a MAP3 kinase linked to at least two MAP kinase cascades and regulatory events that require cytoskeletal reorganization. MEKK1 is activated by molecules that impact cytoskeletal function. MEKK1-/-cells are defective in cell migration, demonstrating that it is required for cell motility. MEKK1 has a 1,200 residue N-terminal regulatory domain that interacts with a dozen identified proteins. Using part of the MEKK1 N-terminus in a yeast two-hybrid screen, we discovered a novel interaction with p115 Rho GTPase-activating protein (GAP). The p115 Rho GAP binds to MEKK1 in vitro and in intact cells. The p115 Rho GAP has selectivity for RhoA over other Rho family members. Expression of p115 Rho GAP reduces MEKK1-induced signaling to AP-1. The reduced activation of AP-1 is dependent on the association of MEKK1 with p115 Rho GAP, because deletion of the Rho GAP SH3 domain, which abrogates their interaction, restores the stimulatory effect of MEKK1 on AP-1 activity. Here we have identified an MEKK1 binding partner that offers a connection between this protein kinase and the machinery regulating cytoskeletal reorganization"
Keywords:		"Amino Acid Sequence Animals Binding Sites Chickens DNA, Complementary/*isolation & purification Dogs GTPase-Activating Proteins/*genetics/metabolism Humans *MAP Kinase Kinase Kinase 1 Mice Molecular Sequence Data Protein Serine-Threonine Kinases/*metaboli;"
Notes:		"MedlineChristerson, Lori B Gallagher, Ewen Vanderbilt, Colleen A Whitehurst, Angelique W Wells, Clark Kazempour, Roxana Sternweis, Paul C Cobb, Melanie H eng Research Support, Non-U.S. Gov't 2002/07/13 J Cell Physiol. 2002 Aug; 192(2):200-8. doi: 10.1002/jcp.10125"