Protein Phosphatase 1-α Regulates AS160 Ser588 and Thr642 Dephosphorylation in Skeletal Muscle.
Protein Phosphatase 1-α Regulates AS160 Ser588 and Thr642 Dephosphorylation in Skeletal Muscle.
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作者：
Sharma P;Arias EB;Cartee GD
Akt substrate of 160 kDa (AS160) phosphorylation on Thr642 and Ser588 by Akt is essential for insulin’s full effect on glucose transport. However, protein phosphorylation is determined by the balance of actions by kinases and phosphatases, and the specific phosphatase(s) controlling AS160 dephosphorylation is (are) unknown. Accordingly, we assessed roles of highly expressed skeletal muscle serine/threonine phosphatases (PP1, PP2A, PP2B, and PP2C) on AS160 dephosphorylation. Preliminary screening of candidate phosphatases used an AS160 dephosphorylation assay. Lysates from insulin-stimulated skeletal muscle were treated with pharmacological phosphatase inhibitors and assessed for AS160 Ser588 and Thr642 dephosphorylation. AS160 dephosphorylation on both phosphorylation sites was unaltered by PP2B or PP2C inhibitors. Okadaic acid (low dose inhibits PP2A; high dose inhibits PP1) delayed AS160 Ser588 (both doses) and Thr642 (high dose only) dephosphorylation concomitant with greater Akt phosphorylation (both doses). AS160 was coimmunoprecipitated with PP1-α but not with PP1-β, PP1-γ1, or PP2A. Recombinant inhibitor-2 protein (a selective PP1 inhibitor) delayed AS160 dephosphorylation on both phosphorylation sites without altering Akt phosphorylation. Furthermore, knockdown of PP1-α but not PP1-β or PP1-γ1 by small interfering RNA caused greater AS160 Ser588 and Thr642 phosphorylation concomitant with unaltered Akt phosphorylation. Together, these results identified PP1-α as a regulator of AS160 Thr642 and Ser588 dephosphorylation in skeletal muscle.
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影响因子：
3.3
作者：
Esteves, Sara L. C.;Domingues, Sara C.;da Cruz e Silva, Edgar F.
通讯作者：
da Cruz e Silva, Edgar F.
影响因子：
4.8
作者：
Hurley, Thomas D.;Yang, Jie;DePaoli-Roach, Anna A.
通讯作者：
DePaoli-Roach, Anna A.
DOI：
10.1152/ajpendo.90581.2008
发表时间：
2009-01-01
影响因子：
5.1
作者：
Ikubo, Mariko;Wada, Tsutomu;Sasaoka, Toshiyasu
通讯作者：
Sasaoka, Toshiyasu
影响因子：
4.4
作者：
Haeseleer，Francoise;Sokal，Izabela;Lee，Amy
通讯作者：
Lee，Amy
影响因子：
5.7
作者：
Cartee GD;Funai K
通讯作者：
Funai K