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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Actin Depolymerizing Factors
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Amino Acid Sequence
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Animals
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Cell Adhesion / physiology
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Cell Line
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Enzyme Activation
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Focal Adhesions / metabolism
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Humans
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Intracellular Signaling Peptides and Proteins
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MAP Kinase Kinase 1 / genetics
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MAP Kinase Kinase 1 / metabolism*
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Microfilament Proteins / metabolism
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Molecular Sequence Data
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Protein Binding
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Proteins / genetics
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Proteins / metabolism
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Rats
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Sequence Alignment
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Signal Transduction / physiology
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Two-Hybrid System Techniques
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p21-Activated Kinases
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rho GTP-Binding Proteins / genetics
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rho GTP-Binding Proteins / metabolism*
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rho-Associated Kinases
Substances
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Actin Depolymerizing Factors
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Adaptor Proteins, Signal Transducing
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Intracellular Signaling Peptides and Proteins
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LAMTOR2 protein, mouse
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Lamtor3 protein, rat
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Microfilament Proteins
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Proteins
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RNA, Small Interfering
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PAK1 protein, human
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Pak1 protein, mouse
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Pak1 protein, rat
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Protein Serine-Threonine Kinases
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p21-Activated Kinases
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rho-Associated Kinases
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Extracellular Signal-Regulated MAP Kinases
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MAP Kinase Kinase 1
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rho GTP-Binding Proteins