The FGF receptor-1 tyrosine kinase domain regulates myogenesis but is not sufficient to stimulate proliferation.
Ligand-stimulated activation of FGF receptors (FGFRs) in skeletal muscle cells represses terminal myogenic differentiation. Skeletal muscle cell lines and subsets of primary cells are dependent on FGFs to repress myogenesis and maintain growth. To understand the intracellular events that transduce these signals, MM14 skeletal muscle cells were transfected with expression vectors encoding chimeric receptors. The chimeras are comprised of the PDGF beta receptor (PDGFbetaR) extracellular domain, the FGFR-1 intracellular domain, and either the PDGFbetaR or FGFR-1 transmembrane domain. The chimeric receptors were autophosphorylated upon PDGF-BB stimulation and are capable of stimulating mitogen-activated protein kinase activity. Activation of the tyrosine kinase domain of either chimera repressed myogenesis, suggesting intracellular responses regulating skeletal muscle differentiation are transduced by activation of the FGFR-1 tyrosine kinase. Unexpectedly, we found that activation of either chimeric receptor failed to stimulate cellular proliferation. Thus, it appears that regulation of skeletal muscle differentiation by FGFs requires only activation of the FGFR tyrosine kinase. In contrast, stimulation of proliferation may require additional, as yet unidentified, signals involving the receptor ectodomain, the FGF ligand, and heparan sulfate either alone, or in combination.
Kudla
A J
AJ
Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907, USA.
Jones
N C
NC
Rosenthal
R S
RS
Arthur
K
K
Clase
K L
KL
Olwin
B B
BB
D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D020797:Receptor, Platelet-Derived Growth Factor beta; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D017468:Receptors, Fibroblast Growth Factor; D014443:Tyrosine; D004247:DNA; C496348:FGFR1 protein, human; C496349:Fgfr1 protein, mouse; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor