FGFR4 and its novel splice form in myogenic cells: Interplay of glycosylation and tyrosine phosphorylation.
The family of fibroblast growth factor receptors (FGFRs) is encoded by four distinct genes. FGFR1 and FGFR4 are both expressed during myogenesis, but whereas the function of FGFR1 in myoblast proliferation has been documented, the role of FGFR4 remains unknown. Here, we report on a new splice form of FGFR4 cloned from primary cultures of mouse satellite cells. This form, named FGFR4(-16), lacks the entire exon 16, resulting in a deletion within the FGFR kinase domain. Expression of FGFR4(-16) coincided with that of wild-type FGFR4 in all FGFR4-expressing tissues examined. Moreover, expression of both FGFR4 forms correlated with the onset of myogenic differentiation, as determined in mouse C2C12 cells and in the inducible myogenic system of 10T(1/2)-MyoD-ER cell line. Both endogenous and overexpressed forms of FGFR4 exhibited N-glycosylation. In contrast to FGFR1, induced homodimerization of FGFR4 proteins did not result in receptor tyrosine phosphorylation. Surprisingly, coexpression of FGFR4 forms and a chimeric FGFR1 protein resulted in FGFR4 tyrosine phosphorylation, raising the possibility that FGFR4 phosphorylation might be enabled by a heterologous tyrosine kinase activity. Collectively, the present study reveals novel characteristics of mouse FGFR4 gene products and delineates their expression pattern during myogenesis. Our findings suggest that FGFR4 functions in a distinctly different manner than the prototype FGFR during myogenic differentiation.
Kwiatkowski
Boguslaw A
BA
Department of Biological Structure, University of Washington School of Medicine, Seattle, Washington 98195, USA.
Kirillova
Irina
I
Richard
Robert E
RE
Israeli
David
D
Yablonka-Reuveni
Zipora
Z
D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D006031:Glycosylation; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D032342:Muscle Cells / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000378:metabolism; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000235:genetics* / Q000378:metabolism*; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000378:metabolism
D018076:DNA, Complementary; D020033:Protein Isoforms; D019000:Phosphotyrosine; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051498:Receptor, Fibroblast Growth Factor, Type 3; D051499:Receptor, Fibroblast Growth Factor, Type 4