Regulation of PPARγ2 Stability and Activity by SHP-1

被引：3

作者：

Kumar, Amit ^{[1
]}

Labrada, Beisy Laborit ^{[1
]}

Lavallee-Bourget, Marie-Helene ^{[1
]}

Forest, Marie-Pier ^{[1
]}

Schwab, Michael ^{[1
]}

Bellmann, Kerstin ^{[1
]}

Houde, Vanessa ^{[1
]}

Beauchemin, Nicole ^{[2
,3
,4
]}

Laplante, Mathieu ^{[1
,5
]}

Marette, Andre ^{[1
,6
]}

机构：

[1] Univ Laval, Ctr Rech Inst Univ Cardiol & Pneumol Quebec CRIUCP, Fac Medecine, Quebec City, PQ, Canada

[2] McGill Univ, Rosalind & Morris Goodman Canc Res Ctr, Dept Oncol, Montreal, PQ, Canada

[3] McGill Univ, Rosalind & Morris Goodman Canc Res Ctr, Dept Med, Montreal, PQ, Canada

[4] McGill Univ, Rosalind & Morris Goodman Canc Res Ctr, Dept Biochem, Montreal, PQ, Canada

[5] Univ Laval, Ctr Rech Canc, Quebec City, PQ, Canada

[6] Laval Univ, Inst Nutr & Funct Foods, Quebec City, PQ, Canada

来源：

MOLECULAR AND CELLULAR BIOLOGY | 2024年 / 44卷 / 07期

基金：

加拿大健康研究院;

关键词：

SHP-1/PTPN6; PPAR gamma 2; protein stability; adipogenesis; PROTEIN-TYROSINE-PHOSPHATASE; ACTIVATED-RECEPTOR-GAMMA; PPAR-GAMMA; DEPENDENT DEGRADATION; CRYSTAL-STRUCTURE; GENE-EXPRESSION; DEPHOSPHORYLATION; PHOSPHORYLATION; BINDING; KINASE;

D O I：

10.1080/10985549.2024.2354959

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The protein tyrosine phosphatase Src homology region 2 domain-containing phosphatase-1 (SHP-1) plays an important role in modulating glucose and lipid homeostasis. We previously suggested a potential role of SHP-1 in the regulation of peroxisome proliferator-activated receptor gamma 2 (PPAR gamma 2) expression and activity but the mechanisms were unexplored. PPAR gamma 2 is the master regulator of adipogenesis, but how its activity is regulated by tyrosine phosphorylation is largely unknown. Here, we found that SHP-1 binds to PPAR gamma 2 primarily via its N-terminal SH2-domain. We confirmed the phosphorylation of PPAR gamma 2 on tyrosine-residue 78 (Y78), which was reduced by SHP-1 in vitro resulting in decreased PPAR gamma 2 stability. Loss of SHP-1 led to elevated, agonist-induced expression of the classical PPAR gamma 2 targets FABP4 and CD36, concomitant with increased lipid content in cells expressing PPAR gamma 2, an effect blunted by abrogation of PPAR gamma 2 phosphorylation. Collectively, we discovered that SHP-1 affects the stability of PPAR gamma 2 through dephosphorylation thereby influencing adipogenesis.

引用

页码：261 / 272

页数：12

共 53 条

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