DEF-1, a novel Src SH3 binding protein that promotes adipogenesis in fibroblastic cell lines

Citation
Fj. King et al., DEF-1, a novel Src SH3 binding protein that promotes adipogenesis in fibroblastic cell lines, MOL CELL B, 19(3), 1999, pp. 2330-2337
Citations number
68
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
MOLECULAR AND CELLULAR BIOLOGY
ISSN journal
0270-7306 → ACNP
Volume
19
Issue
3
Year of publication
1999
Pages
2330 - 2337
Database
ISI
SICI code
0270-7306(199903)19:3<2330:DANSSB>2.0.ZU;2-M
Abstract
The Src homology 3 (SH3) motif is found in numerous signal transduction pro teins involved in cellular growth and differentiation. We have purified and cloned a novel protein, DEF-1 (differentiation-enhancing factor), from bov ine brain by using a Src SH3 affinity column. Ectopic expression of DEF-1 i n fibroblasts resulted in the differentiation of a significant fraction of the culture into adipocytes. This phenotype appears to be related to the in duction of the transcription factor peroxisome proliferator-activated recep tor gamma (PPAR gamma), since DEF-1 NIH 3T3 cells demonstrated augmented le vels of PPAR gamma mRNA and, when treated with activating PPAR gamma ligand s, efficient induction of differentiation. Further evidence for a role for DEF-1 in adipogenesis was provided by heightened expression of DEF-1 mRNA i n 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 mu ltiple tissues, suggesting that the signal transduction pathway(s) in which DEF-1 is involved is not limited to adipogenesis. These results suggest th at 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.