Additive effects of PDGF receptor beta signaling pathways in vascular smooth muscle cell development.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101183755 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1545-7885 (Electronic) Linking ISSN: 15449173 NLM ISO Abbreviation: PLoS Biol Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science, [2003]-

Signal Transduction*; Muscle, Smooth, Vascular/*cytology ; Myocytes, Smooth Muscle/*cytology ; Receptor, Platelet-Derived Growth Factor beta/*physiology; Alleles ; Animals ; Blotting, Southern ; Blotting, Western ; Cytoplasm/metabolism ; Fibroblasts/metabolism ; Immunohistochemistry ; Kidney/metabolism ; Mice ; Mice, Transgenic ; Models, Genetic ; Mutation ; Pericytes/metabolism ; Phenylalanine/chemistry ; Point Mutation ; Protein Structure, Tertiary ; Receptor Protein-Tyrosine Kinases/genetics ; Receptor Protein-Tyrosine Kinases/metabolism ; Receptor, Platelet-Derived Growth Factor beta/genetics ; Retina/embryology ; Time Factors ; Transgenes ; Tyrosine/chemistry

The platelet-derived growth factor beta receptor (PDGFRbeta) is known to activate many molecules involved in signal transduction and has been a paradigm for receptor tyrosine kinase signaling for many years. We have sought to determine the role of individual signaling components downstream of this receptor in vivo by analyzing an allelic series of tyrosine-phenylalanine mutations that prevent binding of specific signal transduction components. Here we show that the incidence of vascular smooth muscle cells/pericytes (v/p), a PDGFRbeta-dependent cell type, can be correlated to the amount of receptor expressed and the number of activated signal transduction pathways. A decrease in either receptor expression levels or disruption of multiple downstream signaling pathways lead to a significant reduction in v/p. Conversely, loss of RasGAP binding leads to an increase in this same cell population, implicating a potential role for this effector in attenuating the PDGFRbeta signal. The combined in vivo and biochemical data suggest that the summation of pathways associated with the PDGFRbeta signal transduction determines the expansion of developing v/p cells.
Competing Interests: The authors have declared that no conflicts of interest exist.

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HD25326 United States HD NICHD NIH HHS; R01 HD025326 United States HD NICHD NIH HHS; R37 HD025326 United States HD NICHD NIH HHS; HD24875 United States HD NICHD NIH HHS; R01 HD024875 United States HD NICHD NIH HHS

42HK56048U (Tyrosine)
47E5O17Y3R (Phenylalanine)
EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta)

Date Created: 20031119 Date Completed: 20060126 Latest Revision: 20181113

20240829

PMC261889

10.1371/journal.pbio.0000052

14624252