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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Publikationen des W. G. Kerckhoff-Instituts     Display Documents



ID: 474465.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Publikationen des W. G. Kerckhoff-Instituts
Semaphorin 4D signaling requires the recruitment of phospholipase C gamma into the plexin-B1 receptor complex
Authors:Swiercz, J. M.; Worzfeld, T.; Offermanns, S.
Date of Publication (YYYY-MM-DD):2009
Title of Journal:Mol Cell Biol
Volume:29
Issue / Number:23
Start Page:6321
End Page:34
Audience:Not Specified
Abstract / Description:The semaphorin 4D (Sema4D) receptor plexin-B1 constitutively interacts with particular Rho guanine nucleotide exchange factors (RhoGEFs) and thereby mediates Sema4D-induced RhoA activation, a process which involves the tyrosine phosphorylation of plexin-B1 by ErbB-2. It is, however, unknown how plexin-B1 phosphorylation regulates RhoGEF activity. We show here that activation of plexin-B1 by Sema4D and its subsequent tyrosine phosphorylation creates docking sites for the SH2 domains of phospholipase Cgamma (PLCgamma). PLCgamma is thereby recruited into the plexin-B1 receptor complex and via its SH3 domain activates the Rho guanine nucleotide exchange factor PDZ-RhoGEF. PLCgamma-dependent RhoGEF activation is independent of its lipase activity. The recruitment of PLCgamma has no effect on the R-Ras GTPase-activating protein activity of plexin-B1 but is required for Sema4D-induced axonal growth cone collapse as well as for the promigratory effects of Sema4D on cancer cells. These data demonstrate a novel nonenzymatic function of PLCgamma as an important mechanism of plexin-mediated signaling which links tyrosine phosphorylation of plexin-B1 to the regulation of a RhoGEF protein and downstream cellular processes.
Free Keywords:Animals; Antigens, CD/*metabolism; Binding Sites; Cell Line; Cell Movement; Enzyme Activation; Growth Cones/metabolism; Guanine Nucleotide Exchange Factors/metabolism; Humans; Nerve Tissue Proteins/genetics/*metabolism; Phospholipase C gamma/*metabolism; Phosphotyrosine/metabolism; Protein Binding; Receptors, Cell Surface/genetics/*metabolism; Semaphorins/*metabolism; *Signal Transduction; ras Proteins/metabolism; rhoA GTP-Binding Protein/metabolism
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:Institute of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, D-69120 Heidelberg, Germany. jakub.swiercz@mpi-bn.mpg.de
Identifiers:ISSN:1098-5549 (Electronic) 1098-5549 (Linking)
URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=..
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