Sally E. Johnson, Ph.D.

The overarching goal of our research program is to define the mechanisms by which intracellular signal transmission controls muscle cell fate.   Skeletal muscle is formed through the fusion of mononucleated precursor myoblasts into large multinucleated myofibers that express the contractile protein machinery.   Proper formation of these large cells is controlled largely through growth factor induced intracellular signaling systems.   Raf is a serine/threonine kinase that causes the sequential phosphorylation of MEK and ERK1/2 thereby, leading to changes in gene transcription.  The absolute amount of Raf/ERK activity dictates the extent of myoblast differentiation and subsequent muscle protein production.   A significant research effort is devoted to manipulating this signaling axis to promote the formation of myofibers as a means of improving muscle size and performance.   In addition, transgenic mice that overexpress components of the Raf signaling system and other transduction pathways are used as models for human skeletal muscle disease and disuse atrophy.  

Representative Publications:

Dorman CM, Johnson SE.  Activated Raf inhibits myogenesis through a mechanism independent of AP-1 mediated myoblast transformation. J Biol Chem 2000; 275:27481-27487.

Becker JR, Dorman CM, McClafferty  TM, Johnson SE.  Characterization of a dominant inhibitory E47 protein that suppresses C2C12 myogenesis.  Exp Cell Res 2001; 267:135-143.

Thomson SR,  Johnson SE.  Isolation and characterization of chicken TaxREB107, a putative DNA binding protein abundantly expressed muscle.  Gene 2001; 278:81-88.

Johnson SE, Dorman CM, Bolanowski SA.  Inhibition of myogenin expression by activated Raf is not responsible for the block to avian myogenesis.  J Biol Chem 2002; 277:28742-28748.

Wang X, Thomson SR, Starkey JD, Page JL, Ealy AD,  Johnson SE.  Transforming growth factor beta-1 (TGF-b1) is up-regulated by activated Raf in skeletal myoblasts but does not contribute to the differentiation-defective phenotype.  J Biol Chem 2003; 279:2528-2534.