PMID- 10067836
OWN - NLM
STAT- MEDLINE
DCOM- 19990323
LR  - 20151119
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 140
IP  - 3
DP  - 1999 Mar
TI  - Pancreatic glucagon-like peptide-1 receptor couples to multiple G proteins and
      activates mitogen-activated protein kinase pathways in Chinese hamster ovary
      cells.
PG  - 1132-40
AB  - Chinese hamster ovary (CHO) cells stably expressing the human insulin receptor
      and the rat glucagon-like peptide-1 (GLP-1) receptor (CHO/GLPR) were used to
      study the functional coupling of the GLP-1 receptor with G proteins and to
      examine the regulation of the mitogen-activated protein (MAP) kinase signaling
      pathway by GLP-1. We showed that ligand activation of GLP-1 receptor led to
      increased incorporation of GTP-azidoanilide into Gs alpha, Gq/11 alpha, and Gi1,2
      alpha, but not Gi3 alpha. GLP-1 increased p38 MAP kinase activity 2.5- and
      2.0-fold over the basal level in both CHO/GLPR cells and rat insulinoma cells
      (RIN 1046-38), respectively. Moreover, GLP-1 induced phosphorylation of the
      immediate upstream kinases of p38, MKK3/MKK6, in CHO/GLPR and RIN 1046-38 cells. 
      Ligand-stimulated GLP-1 receptor produced 1.45- and 2.7-fold increases in
      tyrosine phosphorylation of 42-kDa extracellular signal-regulated kinase (ERK) in
      CHO/GLPR and RIN 1046-38 cells, respectively. In CHO/GLPR cells, these effects of
      GLP-1 on the ERK and p38 MAP kinase pathways were inhibited by pretreatment with 
      cholera toxin (CTX), but not with pertussis toxin. The combination of insulin and
      GLP-1 resulted in an additive response (1.6-fold over insulin alone) that was
      attenuated by CTX. In contrast, the ability of insulin alone to activate these
      pathways was insensitive to either toxin. Our study indicates a direct coupling
      between the GLP-1 receptor and several G proteins, and that CTX-sensitive
      proteins are required for GLP-1-mediated activation of MAP kinases.
FAU - Montrose-Rafizadeh, C
AU  - Montrose-Rafizadeh C
AD  - Laboratory of Clinical Investigation, National Institute on Aging, National
      Institutes of Health, Baltimore, Maryland 21224, USA. montrose@lilly.com
FAU - Avdonin, P
AU  - Avdonin P
FAU - Garant, M J
AU  - Garant MJ
FAU - Rodgers, B D
AU  - Rodgers BD
FAU - Kole, S
AU  - Kole S
FAU - Yang, H
AU  - Yang H
FAU - Levine, M A
AU  - Levine MA
FAU - Schwindinger, W
AU  - Schwindinger W
FAU - Bernier, M
AU  - Bernier M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (GLP1R protein, human)
RN  - 0 (Glp1r protein, rat)
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Receptors, Glucagon)
RN  - EC 2.7.10.1 (Receptor, Insulin)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - AIM
SB  - IM
MH  - Animals
MH  - CHO Cells
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Cloning, Molecular
MH  - Cricetinae
MH  - Enzyme Activation
MH  - GTP-Binding Proteins/*metabolism
MH  - Glucagon-Like Peptide-1 Receptor
MH  - Humans
MH  - *Mitogen-Activated Protein Kinases
MH  - Pancreas/*metabolism
MH  - Rats
MH  - Receptor, Insulin/metabolism
MH  - Receptors, Glucagon/*metabolism
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 1999/03/06 00:00
MHDA- 1999/03/06 00:01
CRDT- 1999/03/06 00:00
PHST- 1999/03/06 00:00 [pubmed]
PHST- 1999/03/06 00:01 [medline]
PHST- 1999/03/06 00:00 [entrez]
AID - 10.1210/endo.140.3.6550 [doi]
PST - ppublish
SO  - Endocrinology. 1999 Mar;140(3):1132-40. doi: 10.1210/endo.140.3.6550.