Adhesion molecule L1 stimulates neuronal migration through Vav2-Pak1 signaling.
Organized neuronal migration and guided axon outgrowth are key determinants of the development of the functional nervous system. L1, a member of the Ig superfamily of cell surface receptors, stimulates cell migration and neurite outgrowth through the MAP kinases ERK1, 2. The signaling molecules participating in this signaling cascade have only partly been identified. Here it is shown that L1 clustering activates the guanine nucleotide exchange factor (GEF) Vav2 and the Rac1 effector p21 associated kinase 1 (Pak1). Also, we found that Pak1 kinase activity contributes to ERK activation by L1, and is necessary for L1-potentiated haptotactic cell migration. A signaling pathway is proposed from L1 through Vav2, Rac1, Pak1 and ERK that may be important for L1 mediated neuronal cell migration.
Schmid
Ralf S
RS
Neuroscience Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7250, USA.
Midkiff
Bentley R
BR
Kedar
Vishram P
VP
Maness
Patricia F
PF
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D039842:Neural Cell Adhesion Molecule L1 / Q000494:pharmacology*; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D015513:Oncogene Proteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051567:Proto-Oncogene Proteins c-vav; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D014162:Transfection / Q000379:methods; D054462:p21-Activated Kinases
D039842:Neural Cell Adhesion Molecule L1; D015513:Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; C490564:Vav2 protein, rat; C515903:PAK1 protein, human; C515906:Pak1 protein, rat; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D020929:Mitogen-Activated Protein Kinase Kinases