title: 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.
authors: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
authors: Margaret Chui Ling
authors: MC
authors: Tse
authors: Xia
authors: X
authors: Liu
authors: Seran
authors: S
authors: Yang
authors: Keqiang
authors: K
authors: Ye
authors: Chi Bun
authors: CB
authors: Chan
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000818:Animals; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010766:Phosphorylation; D051076:Proto-Oncogene Proteins c-fyn / Q000235:genetics / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000378:metabolism*
chemical_list: D020690:GTPase-Activating Proteins; D009419:Nerve Tissue Proteins; D050799:STAT5 Transcription Factor; C494957:FYN protein, human; C494960:Fyn protein, mouse; D053614:Janus Kinase 2; D051076:Proto-Oncogene Proteins c-fyn; C485997:AGAP2 protein, human; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; C529781:PIKE protein, mouse