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Molecular and Cellular Biology, March 1999, p. 2330-2337, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

DEF-1, a Novel Src SH3 Binding Protein That Promotes Adipogenesis in Fibroblastic Cell Lines

Frederick J. King, Erding Hu,dagger David F. Harris, Pasha Sarraf, Bruce M. Spiegelman, and Thomas M. Roberts*

Department of Cancer Biology, The Dana-Farber Cancer Institute, Boston, Massachusetts 02115

Received 10 September 1998/Returned for modification 22 October 1998/Accepted 19 November 1998

The Src homology 3 (SH3) motif is found in numerous signal transduction proteins involved in cellular growth and differentiation. We have purified and cloned a novel protein, DEF-1 (differentiation-enhancing factor), from bovine brain by using a Src SH3 affinity column. Ectopic expression of DEF-1 in fibroblasts resulted in the differentiation of a significant fraction of the culture into adipocytes. This phenotype appears to be related to the induction of the transcription factor peroxisome proliferator-activated receptor gamma  (PPARgamma ), since DEF-1 NIH 3T3 cells demonstrated augmented levels of PPARgamma mRNA and, when treated with activating PPARgamma ligands, efficient induction of differentiation. Further evidence for a role for DEF-1 in adipogenesis was provided by heightened expression of DEF-1 mRNA in adipose tissue isolated from obese and diabetes mice compared to that in tissue isolated from wild-type mice. However, DEF-1 mRNA was detected in multiple tissues, suggesting that the signal transduction pathway(s) in which DEF-1 is involved is not limited to adipogenesis. These results suggest that DEF-1 is an important component of a signal transduction process that is involved in the differentiation of fibroblasts and possibly of other types of cells.

* Corresponding author. Mailing address: Department of Cancer Biology, SM970, The Dana-Farber Cancer Institute, One Jimmy Fund Way, Boston, MA 02115. Phone: (617) 632-3049. Fax: (617) 632-4770. E-mail: thomas_roberts{at}dfci.harvard.edu.

dagger Present address: SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406.

Molecular and Cellular Biology, March 1999, p. 2330-2337, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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