scholarly journals Mitogen-Activated Protein Kinase Kinase (MEK) Activity Is Required for Inhibition of Skeletal Muscle Differentiation by Insulin-Like Growth Factor 1 or Fibroblast Growth Factor 2*

Endocrinology ◽  
1998 ◽  
Vol 139 (4) ◽  
pp. 1794-1800 ◽  
Author(s):  
Crystal M. Weyman ◽  
Alan Wolfman
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Protein Kinase ◽  
Fibroblast Growth Factor ◽  
Mitogen Activated Protein Kinase ◽  
Fibroblast Growth Factor 2 ◽  
Skeletal Muscle Differentiation ◽  
Fibroblast Growth ◽  
Mitogen Activated Protein ◽  
Protein Kinase Kinase

Functional components of basic fibroblast growth factor signaling that inhibit lung elastin gene expression

2001 ◽  
Vol 281 (4) ◽  
pp. L766-L775 ◽  
Author(s):  
Isabel Carreras ◽  
Celeste B. Rich ◽  
Julie A. Jaworski ◽  
Sandra J. Dicamillo ◽  
Mikhail P. Panchenko ◽  
...  
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Fibroblast Growth Factor ◽  
Mitogen Activated Protein Kinase ◽  
Activator Protein 1 ◽  
Fibroblast Growth ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Elastin Gene

Previously, we have demonstrated that basic fibroblast growth factor (bFGF) decreases elastin gene transcription in confluent rat lung fibroblasts via the binding of a Fra-1-c-Jun heterodimer to an activator protein-1-cAMP response element in the distal region of the elastin promoter. In the present study, we show that bFGF activates the mitogen-activated protein kinase extracellular signal-regulated kinase 1/2, resulting in the translocation of phosphorylated extracellular signal-regulated kinase 1/2 into the nucleus followed by increased binding of Elk-1 to the serum response element of the c-Fos promoter, transient induction of c-Fos mRNA, and sustained induction of Fra-1 mRNA. The addition of PD-98059, an inhibitor of mitogen-activated protein kinase kinase, abrogates the bFGF-dependent repression of elastin mRNA expression. Comparative analyses of confluent and subconfluent fibroblast cultures reveal significant differences in elastin mRNA levels and activator protein-1 protein factors involved in the regulation of elastin transcription. These findings suggest that bFGF modulates specific cellular events that are dependent on the state of the cell and provide a rationale for the differential responses that can be expected in development and injury or repair situations.

scholarly journals A Novel Mechanism of Sequestering Fibroblast Growth Factor 2 by Glypican in Lipid Rafts, Allowing Skeletal Muscle Differentiation

2010 ◽  
Vol 30 (7) ◽  
pp. 1634-1649 ◽  
Author(s):  
Jaime Gutiérrez ◽  
Enrique Brandan
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Lipid Rafts ◽  
Muscle Differentiation ◽  
Myoblast Fusion ◽  
Fibroblast Growth Factor 2 ◽  
Skeletal Muscle Differentiation ◽  
Fibroblast Growth ◽  
Raft Domains

ABSTRACT Heparan sulfate proteoglycans (HSPGs) are critical modulators of growth factor activities. Skeletal muscle differentiation is strongly inhibited by fibroblast growth factor 2 (FGF-2). We have shown that HSPGs present at the plasma membrane are expressed in myoblasts and are downregulated during muscle differentiation. An exception is glypican-1, which is present throughout the myogenic process. Myoblasts that do not express glypican-1 exhibit defective differentiation, with an increase in the receptor binding of FGF-2, concomitant with increased signaling. Glypican-1-deficient myoblasts show decreased expression of myogenin, the master gene that controls myogenesis, myosin, and the myoblast fusion index. Reversion of these defects was induced by expression of rat glypican-1. Glypican-1 is the only HSPG localized in lipid raft domains in myoblasts, resulting in the sequestration of FGF-2 away from FGF-2 receptors (FGFRs) located in nonraft domains. A chimeric glypican-1, containing syndecan-1 transmembrane and cytoplasmic domains, is located in nonraft domains interacting with FGFR-IV- and enhanced FGF-2-dependent signaling. Thus, glypican-1 acts as a positive regulator of muscle differentiation by sequestering FGF-2 in lipid rafts and preventing its binding and dependent signaling.

scholarly journals Fibroblast Growth Factor Homologous Factors and the Islet Brain-2 Scaffold Protein Regulate Activation of a Stress-activated Protein Kinase

2002 ◽  
Vol 277 (51) ◽  
pp. 49111-49119 ◽  
Author(s):  
Jon Schoorlemmer ◽  
Mitchell Goldfarb
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Fibroblast Growth Factor ◽  
Scaffold Protein ◽  
Adult Brain ◽  
Mitogen Activated Protein Kinase ◽  
Fibroblast Growth ◽  
Mitogen Activated Protein ◽  
Mixed Lineage Kinase 3

Fibroblast growth factor homologous factors (FHFs) form native intracellular complexes with the mitogen-activated protein kinase (MAPK) scaffold protein islet-brain 2 (IB2) in adult brain. FHF binding to IB2 facilitates recruitment of the MAPK p38δ (SAPK4), while failing to stimulate binding of JNK, the preferred kinase of the related scaffold IB1 (JIP-1). We now report further biochemical evidence supporting FHFs as regulators of IB2 scaffold activity. Mixed lineage kinase 3 (MLK3) and IB2 synergistically activate p38δ but not the MAPKs JNK-1 and p38α. Binding of p38δ to IB2 is mediated by the carboxyl-terminal half of the scaffold (IB2Δ1–436). FHF2 also binds weakly to IB2Δ1–436and can thereby increase p38δ interaction with IB2Δ1–436. FHF-induced recruitment of p38δ to IB2 is accompanied by increased levels of activated p38δ, and synergistic activation of p38δ by MLK3 and IB2 is further enhanced by FHF2. Consistent with a role for FHFs as signaling molecules, FHF2 isolated from rat brain is serine/threonine-phosphorylated, and FHF can serve as a substrate for p38δin vitro. These results support the existence of a signaling module in which IB2 scaffolds a MLK3/MKK/p38δ kinase cascade. FHFs aid in recruitment of p38 to IB2 and may serve as kinase substrates.

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