Glycogen synthase kinase-3 is the predominant insulin-regulated eukaryotic initiation factor 2B kinase in skeletal muscle.

摘要: Abstract Eukaryotic initiation factor eIF2B is a guanine nucleotide exchange protein involved in regulation of translation initiation. Phosphorylation the e-subunit thought to be important insulin-mediated changes activity. However, elucidation insulin's action has proven elusive, primarily because eIF2Be substrate vitro for at least three different kinases. In present study, we observed kinase activity only those muscles previously shown exhibit alterations synthesis response insulin. Specifically, was increased psoas muscle from diabetic rats compared controls. Treating with insulin rapidly reduced below control values. Changes were not heart. To identify kinase(s) responsible phosphorylating eIF2Be, wildtype and two variant forms expressed purified Sf9 insect cells, used as substrates assays. The first contained point mutation cDNA that converted glycogen synthase kinase-3 (GSK-3) phosphorylation site, Ser535, nonphosphorylatable Ala residue. second variant, putative GSK-3 `priming' Ser539, Asp. Based on pattern using casein (CK)-I, CK-II, or well skeletal extracts, conclude predominant GSK-3. Thus, are likely involve