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The MEK1 scaffolding protein MP1 regulates cell spreading by integrating PAK1 and Rho signals

Item Type:Article
Title:The MEK1 scaffolding protein MP1 regulates cell spreading by integrating PAK1 and Rho signals
Creators Name:Pullikuth, A. and McKinnon, E. and Schaeffer, H.J. and Catling, A.D.
Abstract: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. Copyright
Keywords:Actin Depolymerizing Factors, Amino Acid Sequence, Cell Adhesion, Cell Line, Enzyme Activation, Extracellular Signal-Regulated MAP Kinases, Focal Adhesions, Intracellular Signaling Peptides and Proteins, MAP Kinase Kinase 1, Microfilament Proteins, Molecular Sequence Data, Protein Binding, Protein-Serine-Threonine Kinases, Proteins, Rho GTP-Binding Proteins, Sequence Alignment, Signal Transduction, Signal Transducing Adaptor Proteins, Small Interfering RNA, Two-Hybrid System Techniques, Animals, Rats
Source:Molecular and Cellular Biology
ISSN:0270-7306
Publisher:American Society for Microbiology (U.S.A.)
Volume:25
Number:12
Page Range:5119-5133
Date:1 June 2005
Official Publication:https://doi.org/10.1128/MCB.25.12.5119-5133.2005
PubMed:View item in PubMed

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