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We previously identified km23 as a novel TGFbeta receptor-interacting protein. Here we show that km23 is ubiquitously expressed in human tissues and that cell-type specific differences in endogenous km23 protein expression exist. In addition, we demonstrate that the phosphorylation of km23 is TGFbeta-dependent, in that EGF was unable to phosphorylate km23. Further, the kinase activity of both TGFbeta receptors appears to play a role in the TGFbeta-mediated phosphorylation of km23, although TGFbeta RII kinase activity is absolutely required for km23 phosphorylation. Blockade of km23 using small interfering RNAs significantly decreased key TGFbeta responses, including induction of fibronectin expression and inhibition of cell growth. Thus, our results demonstrate that km23 is required for TGFbeta induction of fibronectin expression and is necessary, but not sufficient, for TGFbeta-mediated growth inhibition.
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