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© The Rockefeller University Press, 0021-9525/1998//241 $5.00
The Journal of Cell Biology, Volume 142, Number 1, , 1998 241-250

The FGF Receptor–1 Tyrosine Kinase Domain Regulates Myogenesis but Is Not Sufficient to Stimulate Proliferation

Arthur J. Kudla, Nathan C. Jones^*, R. Scott Rosenthal^*, Kirstin Arthur^||, Kari L. Clase, and Bradley B. Olwin^*

^* Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado 80309, and the Walther Cancer Institute, Indianapolis, Indiana 47238; Department of Biological Sciences, Department of Basic Medical Sciences, and ^|| Department of Biochemistry, Purdue University, West Lafayette, Indiana 47907

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 β receptor (PDGFβR) extracellular domain, the FGFR-1 intracellular domain, and either the PDGFβR 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.

Key Words: skeletal muscle • differentiation • fibroblast growth factor • myogenesis • tyrosine kinase

Abbreviations used in this paper: BrdU, 5-bromo-2 deoxyuridine; CMV, cytomegalovirus; ERK, extracellular-regulated kinase; FGFR, FGF receptor; MAPK, mitogen-activated protein kinase; MBP, myelin basic protein; MHC, myosin heavy chain; PDGFβR, PDGF β receptor; PR_tm/FR1, PDGFβR/FGFR-1 chimera with PDGFβR transmembrane domain; PR/ FR1_tm, PDGFβR/FGFR-1 chimera with FGFR-1 transmembrane domain; RT, reverse transcription; TPA, 12-O-tetra-decnoylphorbol-13-acetate.

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