SHP-2 positively regulates adipogenic differentiation in 3T3-L1 cells.
The Src homology domain 2 (SH2)-containing tyrosine phosphatase SHP-2 has been implicated in the regulation of proliferation and differentiation in various cell types. Here, we investigated the ability of SHP-2 to mediate insulin-induced adipogenic differentiation of mouse 3T3-L1 cells. We found that the expression of SHP-2 was increased along with adipogenic differentiation. Overexpression of wild-type SHP-2 in 3T3-L1 cells resulted in enhanced adipocyte differentiation. Furthermore, insulin-stimulated adipogenic differentiation of 3T3-L1 cells was abolished by down-regulating SHP-2 expression using short interfering RNA. These results suggest that SHP-2 is a positive effector in signal transduction pathways necessary for adipocyte differentiation. In SHP-2 knockdown cells, the expression of peroxisome proliferator-activated receptor gamma, a master regulator of adipogenesis, was entirely suppressed even in the late phase of differentiation, whereas the expression level of C/EBPdelta was unchanged. These results highlight a novel role of SHP-2 in the signal transduction pathways regulating adipocyte differentiation.
Uehara
Takuya
T
Laboratory of Molecular Medicinal Sciences, Department of Bioscience and Bioinformatics, College of Information Science and Engineering, Ritsumeikan University, Shiga 525-8577, Japan.
Suzuki
Kenji
K
Yamanaka
Hideyuki
H
Kizaki
Takako
T
Sakurai
Takuya
T
Ishibashi
Yoshinaga
Y
Ishida
Hitoshi
H
Ohno
Hideki
H
D041721:3T3-L1 Cells / Q000166:cytology* / Q000187:drug effects; D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D030781:Organisms, Genetically Modified; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000502:physiology*
D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse