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Identification and distribution of a novel platelet-derived growth factor receptor beta variant: effect of retinoic acid and involvement in cell differentiation.

Wang Y, Culty M

Department of Biochemistry and Molecular and Cellular Biology, Georgetown University Medical Center, Washington, D.C. 20057, USA.

We have shown previously that neonatal testicular gonocytes express platelet-derived growth factor receptors (PDGFR) alpha and beta. We report the expression of a novel PDGFRbeta (V1-PDGFRbeta) transcript in gonocytes of 3-d-old rat testes. V1-PDGFRbeta nucleotide sequence spans from intron 6 to exon 23 of the PDGFRbeta gene, and is predicted to encode a protein lacking part of the extracellular domain. V1-PDGFRbeta transcripts are expressed preferentially in developing gonads. The embryonic teratocarcinoma F9 cells, in which differentiation is driven by retinoic acid (RA), express V1-PDGFRbeta, but not wild-type PDGFRbeta. Green fluorescent protein-tagged V1-PDGFRbeta localized mainly in cytosol of F9, MA-10, and COS-1 cells. FLAG and green fluorescent protein-tagged V1-PDGFRbeta displayed tyrosine kinase activities and contain phosphotyrosine residues, suggesting that V1-PDGFRbeta is a cytosolic tyrosine kinase. Treatment of F9 cells with RA induced V1-PDGFRbeta gene expression, concomitant with changes in morphology and increased mRNA expression of collagen IV and laminin B1, suggesting that V1-PFGRbeta is involved in cell differentiation. Similarly, treatment of postnatal d 3 rat gonocytes with RA induced a dose-dependent increase in V1-PDGFRbeta expression together with an increase in c-kit and Stra8, markers of more differentiated germ cells and a concomitant decrease in GFRalpha1, a marker of spermatogonial stem cells. However, an excess of V1-PDGFRbeta inhibited RA-mediated collagen IV and laminin B1 expression and altered both RA-dependent and RA-independent morphological changes in F9 cells, while increasing cell survival. These results suggest that the expression of V1-PDGFRbeta is tightly regulated during differentiation and that it may play an active role in germ cell differentiation.

Published 20 April 2007 in Endocrinology, 148(5): 2233-50.
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