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PMID: 8668187 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Actions of Rho family small G proteins and p21-activated protein kinases on mitogen-activated protein kinase family members.

Molecular and cellular biology ·Vol. 16 ·No. 7 ·1996-07-00 ·Pages 3707-13

Frost JA, Xu S, Hutchison MR, Marcus S, Cobb MH

Abstract

The mitogen-activated protein (MAP) kinases are a family of serine/threonine kinases that are regulated by distinct extracellular stimuli. The currently known members include extracellular signal-regulated protein kinase 1 (ERK1), ERK2, the c-Jun N-terminal kinase/stress-activated protein kinases (JNK/SAPKs), and p38 MAP kinases. We find that overexpression of the Ste20-related enzymes p21-activated kinase 1 (PAK1) and PAK2 in 293 cells is sufficient to activate JNK/SAPK and to a lesser extent p38 MAP kinase but not ERK2. Rat MAP/ERK kinase kinase 1 can stimulate the activity of each of these MAP kinases. Although neither activated Rac nor the PAKs stimulate ERK2 activity, overexpression of either dominant negative Rac2 or the N-terminal regulatory domain of PAK1 inhibits Ras-mediated activation of ERK2, suggesting a permissive role for Rac in the control of the ERK pathway. Furthermore, constitutively active Rac2, Cdc42hs, and RhoA synergize with an activated form of Raf to increase ERK2 activity. These findings reveal a previously unrecognized connection between Rho family small G proteins and the ERK pathway.

MeSH Terms
Animals Base Sequence Calcium-Calmodulin-Dependent Protein Kinases/metabolism Cell Line Cloning, Molecular Culture Media, Conditioned DNA Primers Enzyme Activation GTP-Binding Proteins/metabolism Humans Intracellular Signaling Peptides and Proteins MAP Kinase Kinase Kinases Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases Molecular Sequence Data Mutagenesis, Site-Directed Protein Serine-Threonine Kinases/metabolism Protein-Tyrosine Kinases/metabolism Rats Recombinant Proteins/metabolism Saccharomyces cerevisiae Proteins Substrate Specificity Transfection p21-Activated Kinases
Chemicals
Culture Media, Conditioned DNA Primers Intracellular Signaling Peptides and Proteins Recombinant Proteins Saccharomyces cerevisiae Proteins Protein-Tyrosine Kinases PAK1 protein, human Pak1 protein, rat Protein Serine-Threonine Kinases p21-Activated Kinases Calcium-Calmodulin-Dependent Protein Kinases Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases MAP Kinase Kinase Kinases STE20 protein, S cerevisiae GTP-Binding Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Frost J A
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, 75235-9041, USA.
Xu S
Hutchison M R
Marcus S
Cobb M H
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46 references, click to expand
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.16.7.3707
Published
1996-07-00
Pages
3707-13
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC231366
Subset
IM
Grants
NIGMS NIH HHS · F32 GM016926 · United States
NIDDK NIH HHS · DK34128 · United States
NIGMS NIH HHS · GM16926 · United States
NIGMS NIH HHS · GM53032 · United States
External Links
PubMed source DOI: 10.1128/MCB.16.7.3707 PMC Full Text View journal details
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