B plexins activate Rho through PDZ-RhoGEF.
Plexins are receptors for the repulsive axon guidance molecules semaphorins. Previously, we have shown that plexin-B1 binds activated Rac, but that clustering of plexin-B1 causes Rho activation, resulting in stress fiber formation. Using the yeast two-hybrid system, we found that the C-terminus of B plexins interacted directly with Rho-specific exchange factors, via their PDZ domain. Mutation of the carboxy-terminal amino acids of plexin-B1 or coexpression of a dominant negative PDZ-RhoGEF abrogated the ability of plexin-B1 to cause stress fiber formation. Our results demonstrate a role for PDZ-RhoGEF in B plexin-mediated activation of Rho/Rho kinase signaling, implicated in the regulation of axon guidance and cell migration.
Driessens
Mariette H E
MH
Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. mariette@niob.knaw.nl
Olivo
Cristina
C
Nagata
Koh-ichi
K
Inagaki
Masaki
M
Collard
John G
JG
D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D020798:Two-Hybrid System Techniques
D020662:Guanine Nucleotide Exchange Factors; D009419:Nerve Tissue Proteins; C492119:PLXNB1 protein, human; C492118:Plxnb1 protein, mouse; C403525:RAPGEF2 protein, human; D011956:Receptors, Cell Surface; D019204:GTP-Binding Proteins