Fyn Regulates Adipogenesis by Promoting PIKE-A/STAT5a Interaction

Abstract

Fyn is a tyrosine kinase with multiple roles in a variety of cellular processes. Here we report that Fyn is a new kinase involved in adipocyte differentiation. Elevated Fyn protein is detected specifically in the adipocytes of obese mice. Moreover, Fyn expression increases progressively in 3T3-L1 cells during in vitro adipogenesis, which correlates with its kinase activity. Inhibition of Fyn by either genetic or pharmacological manipulation restrains the 3T3-L1 preadipocytes from fully differentiating into mature adipocytes. Mechanistically, Fyn regulates the activity of the adipogenic transcription factor signal transducer and activator of transcription 5a (STAT5a) through enhancing its interaction with the GTPase phosphoinositide 3-kinase enhancer A (PIKE-A). The STAT5a activity is therefore reduced in Fyn- or PIKE-ablated adipose tissues, leading to diminished expression of adipogenic markers and adipocyte differentiation. Our data thus demonstrate a novel functional interaction between Fyn, PIKE-A, and STAT5a in mediating adipogenesis.

ACKNOWLEDGMENTS

We are grateful to N. C. Reich (Stony Brook University, NY) for the GFP-STAT5a plasmid and C. Schindler (Columbia University, NY) for the GFP-STAT3 plasmid. We also thank Obiamaka Okianyo (Emory University, Atlanta, GA) for her critical reading of the manuscript.

This work is supported by grant R01-NS045627 from the NIH to K. Ye and the URC grant 00016337 from Emory University to C. B. Chan.