Abstract:
:Platelet-derived growth factor receptor (PDGFR) signaling is essential for normal embryonic development in many organisms, including frog, mouse, zebrafish, and sea urchin. The mode of action of PDGFR signaling during early development is poorly understood, however, mostly because inhibition of signaling through either the PDGFRalpha or PDGFRbeta is embryonic lethal. In Xenopus embryos, disruption of PDGFRalpha signaling causes migrating anterior mesoderm cells to lose direction and undergo apoptosis through the mitochondrial pathway. To understand the mechanism of PDGFRalpha function in this process, we have analyzed all known effector-binding sites in vivo. By using a chemical inducer of dimerization to activate chimera PDGFRalphas, we have identified a role for phospholipase Cgamma (PLCgamma) in protecting cells from death. PDGFRalpha-mediated cell survival requires PLCgamma and phosphatidylinositol 3-kinase signaling, and that PDGFRalpha with binding sites for these two signaling factors is sufficient for this activity. Other effectors of PDGFRalpha signaling, Shf, SHP-2, and Crk, are not required for this process. Thus, our findings show that PDGFRalpha signaling through PLCgamma and phosphatidylinositol 3-kinase has a protective role in preventing apoptosis in early development. Furthermore, we demonstrate that small molecule inducers of dimerization provide a powerful system to manipulate receptor function in developing embryos.
journal_name
Proc Natl Acad Sci U S Aauthors
Van Stry M,Kazlauskas A,Schreiber SL,Symes Kdoi
10.1073/pnas.0502885102keywords:
subject
Has Abstractpub_date
2005-06-07 00:00:00pages
8233-8issue
23eissn
0027-8424issn
1091-6490pii
0502885102journal_volume
102pub_type
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