The MEK1 scaffolding protein MP1 regulates cell spreading by integrating PAK1 and Rho signals.
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.
Pullikuth
Ashok
A
Department of Pharmacology, Louisiana State University Health Sciences Center, 1901 Perdido Street, New Orleans, LA 70112, USA.
McKinnon
Evangeline
E
Schaeffer
Hans-Joerg
HJ
Catling
Andrew D
AD
D051339:Actin Depolymerizing Factors; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D048369:MAP Kinase Kinase 1 / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology; D020798:Two-Hybrid System Techniques; D054462:p21-Activated Kinases; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D054460:rho-Associated Kinases
D051339:Actin Depolymerizing Factors; D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; C426009:LAMTOR2 protein, mouse; C501973:Lamtor3 protein, rat; D008840:Microfilament Proteins; D011506:Proteins; D034741:RNA, Small Interfering; C515903:PAK1 protein, human; C515905:Pak1 protein, mouse; C515906:Pak1 protein, rat; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D054460:rho-Associated Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048369:MAP Kinase Kinase 1; D020741:rho GTP-Binding Proteins