TY - JOUR
T1 - Regulation of ERK1 and ERK2 by glucose and peptide hormones in pancreatic β cells
AU - Arnette, Don
AU - Gibson, Tara Beers
AU - Lawrence, Michael C.
AU - January, Bridgette
AU - Khoo, Shih
AU - McGlynn, Kathleen
AU - Vanderbilt, Colleen A.
AU - Cobb, Melanie H.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2003/8/29
Y1 - 2003/8/29
N2 - We showed previously that ERK1/2 were activated by glucose and amino acids in pancreatic β cells. Here we examine and compare signaling events that are necessary for ERK1/2 activation by glucose and other stimuli in β cells. We find that agents that interrupt Ca2+ signaling by a variety of mechanisms interfere with glucose- and glucagon-like peptide (GLP-1)-stimulated ERK1/2 activity. In particular, calmodulin antagonists, FK506, and cyclosporin, immunosuppressants that inhibit the calcium-dependent phosphatase calcineurin, suppress ERK1/2 activation by both glucose and GLP-1. Ca2+ signaling from intracellular stores is also essential for ERK1/ 2 activation, because thapsigargin blocks ERK1/2 activation by glucose or GLP-1. The glucosesensitive mechanism is distinct from that used by phorbol ester or insulin to stimulate ERK1/2 but shares common features with that used by GLP-1.
AB - We showed previously that ERK1/2 were activated by glucose and amino acids in pancreatic β cells. Here we examine and compare signaling events that are necessary for ERK1/2 activation by glucose and other stimuli in β cells. We find that agents that interrupt Ca2+ signaling by a variety of mechanisms interfere with glucose- and glucagon-like peptide (GLP-1)-stimulated ERK1/2 activity. In particular, calmodulin antagonists, FK506, and cyclosporin, immunosuppressants that inhibit the calcium-dependent phosphatase calcineurin, suppress ERK1/2 activation by both glucose and GLP-1. Ca2+ signaling from intracellular stores is also essential for ERK1/ 2 activation, because thapsigargin blocks ERK1/2 activation by glucose or GLP-1. The glucosesensitive mechanism is distinct from that used by phorbol ester or insulin to stimulate ERK1/2 but shares common features with that used by GLP-1.
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U2 - 10.1074/jbc.M301174200
DO - 10.1074/jbc.M301174200
M3 - Article
C2 - 12783880
AN - SCOPUS:0041375468
SN - 0021-9258
VL - 278
SP - 32517
EP - 32525
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 35
ER -