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| Content Provider | PubMed Central |
|---|---|
| Author | Swiercz, Jakub M. Thomas, Worzfeld Offermanns, Stefan |
| Copyright Year | 2009 |
| Abstract | 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 Cγ (PLCγ). PLCγ is thereby recruited into the plexin-B1 receptor complex and via its SH3 domain activates the Rho guanine nucleotide exchange factor PDZ-RhoGEF. PLCγ-dependent RhoGEF activation is independent of its lipase activity. The recruitment of PLCγ 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 PLCγ 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. |
| Related Links | http://dx.doi.org/10.1128/MCB.00103-09 |
| Starting Page | 6321 |
| File Format | |
| ISSN | 10985549 |
| e-ISSN | 10985549 |
| Journal | Molecular and Cellular Biology |
| Issue Number | 23 |
| Volume Number | 29 |
| Language | English |
| Publisher | American Society for Microbiology (ASM) |
| Publisher Date | 2009-12-01 |
| Access Restriction | Open |
| Rights Holder | American Society for Microbiology (ASM) |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Molecular Biology |
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