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Molecular and Cellular Biology, June 2005, p. 5119-5133, Vol. 25, No. 12
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.12.5119-5133.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The MEK1 Scaffolding Protein MP1 Regulates Cell Spreading by Integrating PAK1 and Rho Signals

Ashok Pullikuth,1 Evangeline McKinnon,1 Hans-Joerg Schaeffer,2,{dagger} and Andrew D. Catling1,3*

Department of Pharmacology,1 Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, 1901 Perdido Street, New Orleans, Louisiana 70112,3 Department of Microbiology, University of Virginia, Charlottesville, Virginia 229082

Received 7 July 2004/ Returned for modification 19 August 2004/ Accepted 17 March 2005

How the extracellular signal-regulated kinase (ERK) cascade regulates diverse cellular functions, including cell proliferation, survival, and motility, in a context-dependent manner remains poorly understood. Compelling evidence indicates that scaffolding molecules function in yeast to channel specific signals through common components to appropriate targets. Although a number of putative ERK scaffolding proteins have been identified in mammalian systems, none has been linked to a specific biological response. Here we show that the putative scaffold protein MEK partner 1 (MP1) and its partner p14 regulate PAK1-dependent ERK activation during adhesion and cell spreading but are not required for ERK activation by platelet-derived growth factor. MP1 associates with active but not inactive PAK1 and controls PAK1 phosphorylation of MEK1. Our data further show that MP1, p14, and MEK1 serve to inhibit Rho/Rho kinase functions necessary for the turnover of adhesion structures and cell spreading and reveal a signal-channeling function for a MEK1/ERK scaffold in orchestrating cytoskeletal rearrangements important for cell motility.


* Corresponding author. Mailing address: Department of Pharmacology and Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, 1901 Perdido Street, New Orleans, LA 70112. Phone: (504) 568-4740. Fax: (504) 568-2361. E-mail: acatli{at}lsuhsc.edu.

{dagger} Current address: Department of Cell Biology, Max Delbrück Center, Robert-Roessle-Str. 10, Berlin 13092, Germany.


Molecular and Cellular Biology, June 2005, p. 5119-5133, Vol. 25, No. 12
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.12.5119-5133.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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