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Published online 30 October 2006. doi:10.1083/jcb.200608031
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 175, Number 3, 383-388
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 Activation of p38{alpha}/ß MAPK in myogenesis via binding of the scaffold protein JLP to the cell surface protein Cdo

Giichi Takaesu1, Jong-Sun Kang1, Gyu-Un Bae1, Min-Jeong Yi1, Clement M. Lee2, E. Premkumar Reddy2, and Robert S. Krauss1

1 Brookdale Department of Molecular, Cell, and Developmental Biology, Mount Sinai School of Medicine, New York, NY 10029
2 Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140

Correspondence to Robert S. Krauss: Robert.Krauss{at}mssm.edu

The p38 mitogen-activated protein kinase (MAPK) pathway plays an important role in cell differentiation, but the signaling mechanisms by which it is activated during this process are largely unknown. Cdo is an immunoglobulin superfamily member that functions as a component of multiprotein cell surface complexes to promote myogenesis. In this study, we report that the Cdo intracellular region interacts with JLP, a scaffold protein for the p38{alpha}/ß MAPK pathway. Cdo, JLP, and p38{alpha}/ß form complexes in differentiating myoblasts, and Cdo and JLP cooperate to enhance levels of active p38{alpha}/ß in transfectants. Primary myoblasts from Cdo–/– mice, which display a defective differentiation program, are deficient in p38{alpha}/ß activity, and the expression of an activated form of MKK6 (an immediate upstream activator of p38) rescues the ability of Cdo–/– cells to differentiate. These results document a novel mechanism of signaling during cell differentiation: the interaction of a MAPK scaffold protein with a cell surface receptor.

G. Takaesu and J.-S. Kang contributed equally to this paper.

G. Takaesu's current address is Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.

Abbreviations used in this paper: DM, differentiation medium; GM, growth medium; MHC, myosin heavy chain.


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