Requirement of SRC-family tyrosine kinases in fat accumulation.
Src-family tyrosine kinases mediate many receptor signals to various biological responses. Here we investigate the requirement of Src-family tyrosine kinases in adipogenesis. The biochemical mechanism by which insulin induces adipogenesis, converting fibroblast cells to adipocytes, is not clear. We show that fibroblast cells deficient of three ubiquitously expressed Src-family members (Src, Yes, and Fyn), SYF cells, are refractory to hormonally induced fat accumulation. The defect is rescued by reintroduction of c-Src into SYF cells. Furthermore, Src-family tyrosine kinases are required in the early steps of insulin signaling; it is responsible for the tyrosine phosphorylation of adaptor protein c-Cbl. Deficiency of c-Cbl blocked adipogenesis. These genetic and biochemical data clearly demonstrate that Src-family tyrosine kinases serve as a critical signal relay, via phosphorylation of c-Cbl, for fat accumulation, and provide potential new strategies for treating obesity.
Sun
Yutong
Y
Department of Physiology, Weill Medical College, Cornell University, New York, New York 10021, USA.
Ma
Yong-Chao
YC
Huang
Jianyun
J
Chen
Krystina Y
KY
McGarrigle
Deirdre K
DK
Huang
Xin-Yun
XY
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
D007328:Insulin; D047495:PPAR gamma; D019061:src-Family Kinases