Phosphorylation of the skeletal muscle glycogen-targetting subunit of protein phosphatase 1 in response to adrenaline in vivo.
The protein G(M), which targets protein phosphatase 1 (PP1) to the glycogen particles and sarcoplasmic reticulum (SR) of striated muscles, is known to be phosphorylated at Ser48 and Ser67 in vitro by adenosine 3',5' cyclic monophosphate-dependent protein kinase (PKA) and at Ser48 by MAP kinase-activated protein kinase-1 (MAPKAP-K1, also called p90 RSK). The phosphorylation of Ser48 increases the rate at which the glycogen-associated PP1.G(M) complex dephosphorylates (activates) glycogen synthase, but the phosphorylation of Ser67 has the opposite effect, suppressing the activity of PP1 toward glycogen-bound substrates. The phosphorylation of Ser67 overrides the activating effect of Ser48 phosphorylation because it dissociates PP1 from G(M). Here, we use two phospho-specific antibodies to demonstrate that the SR-associated form of G(M), as well as the glycogen-associated form of G(M), becomes phosphorylated at Ser48 and Ser67 in response to adrenaline, supporting the view that the PKA-mediated regulation of the PP1.G(M) complex plays a role in the adrenergic control of glycogen metabolism and SR function. In contrast, Ser48 is not phosphorylated significantly in response to insulin, and neither is Ser67. Thus the phosphorylation of G(M) at Ser48 by MAPKAP-K1 or other insulin-stimulated protein kinases is not involved in the activation of glycogen synthase by insulin.
Walker
K S
KS
MRC Protein Phosphorylation Unit, MSI/WTB Complex, University of Dundee, Dow Street, Dundee, UK.
Watt
P W
PW
Cohen
P
P
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D004837:Epinephrine / Q000494:pharmacology*; D006003:Glycogen / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology*; D010749:Phosphoprotein Phosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D054645:Protein Phosphatase 1; D020836:Protein Structure, Quaternary; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000201:enzymology; D012694:Serine / Q000737:chemistry
D007328:Insulin; D012694:Serine; D006003:Glycogen; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D004837:Epinephrine