Article

Involvement of MAPK signaling molecules and Runx2 in the NELL1-induced osteoblastic differentiation.

Department of Structural Molecular Biology, The Institute of Scientific and Industrial Research, Osaka University, Osaka, Japan.
FEBS Letters (impact factor: 3.54). 02/2008; 582(2):365-71. DOI:10.1016/j.febslet.2007.12.006 pp.365-71
Source: PubMed

ABSTRACT NELL1 is an extracellular protein inducing osteogenic differentiation and bone formation of osteoblastic cells. To elucidate the intracellular signaling cascade evoked by NELL1, we have shown that NELL1 protein transiently activates the MAPK signaling cascade, induces the phosphorylation of Runx2, and promotes the rapid intracellular accumulation of Tyr-phosphorylated proteins. Unlike BMP2, NELL1 protein does not activate the Smad signaling cascade. These findings suggest that upon binding to a specific receptor NELL1 transduces an osteogenic signal through activation of certain Tyr-kinases associated with the Ras-MAPK cascade, and finally leads to the osteogenic differentiation.

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Keywords

bone formation
 
certain Tyr-kinases
 
extracellular protein inducing osteogenic differentiation
 
intracellular signaling cascade evoked
 
MAPK signaling cascade
 
phosphorylation
 
promotes
 
rapid intracellular accumulation
 
Ras-MAPK cascade
 
specific receptor NELL1 transduces
 
Tyr-phosphorylated proteins