p115 Rho GTPase activating protein interacts with MEKK1

Lori B. Christerson, Ewen Gallagher, Colleen A. Vanderbilt, Angelique W. Whitehurst, Clark Wells, Roxana Kazempour, Paul C. Sternweis, Melanie H. Cobb

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)200-208
Number of pages9
JournalJournal of Cellular Physiology
Volume192
Issue number2
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

MAP Kinase Kinase Kinase 1
Transcription Factor AP-1
Yeast
Cell Movement
rho GTPase-activating protein
Yeasts
MAP Kinase Kinase Kinases
src Homology Domains
MAP Kinase Signaling System
Pheromones
Protein Kinases
Machinery

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Christerson, L. B., Gallagher, E., Vanderbilt, C. A., Whitehurst, A. W., Wells, C., Kazempour, R., ... Cobb, M. H. (2002). p115 Rho GTPase activating protein interacts with MEKK1. Journal of Cellular Physiology, 192(2), 200-208. https://doi.org/10.1002/jcp.10125

p115 Rho GTPase activating protein interacts with MEKK1. / Christerson, Lori B.; Gallagher, Ewen; Vanderbilt, Colleen A.; Whitehurst, Angelique W.; Wells, Clark; Kazempour, Roxana; Sternweis, Paul C.; Cobb, Melanie H.

In: Journal of Cellular Physiology, Vol. 192, No. 2, 2002, p. 200-208.

Research output: Contribution to journalArticle

Christerson, LB, Gallagher, E, Vanderbilt, CA, Whitehurst, AW, Wells, C, Kazempour, R, Sternweis, PC & Cobb, MH 2002, 'p115 Rho GTPase activating protein interacts with MEKK1', Journal of Cellular Physiology, vol. 192, no. 2, pp. 200-208. https://doi.org/10.1002/jcp.10125
Christerson LB, Gallagher E, Vanderbilt CA, Whitehurst AW, Wells C, Kazempour R et al. p115 Rho GTPase activating protein interacts with MEKK1. Journal of Cellular Physiology. 2002;192(2):200-208. https://doi.org/10.1002/jcp.10125
Christerson, Lori B. ; Gallagher, Ewen ; Vanderbilt, Colleen A. ; Whitehurst, Angelique W. ; Wells, Clark ; Kazempour, Roxana ; Sternweis, Paul C. ; Cobb, Melanie H. / p115 Rho GTPase activating protein interacts with MEKK1. In: Journal of Cellular Physiology. 2002 ; Vol. 192, No. 2. pp. 200-208.
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