PMID- 9133538
OWN - NLM
STAT- MEDLINE
DCOM- 19970528
LR  - 20211203
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 46
IP  - 5
DP  - 1997 May
TI  - Differential activation of mitogen-activated protein kinase by insulin and 
      epidermal growth factor in 3T3-L1 adipocytes: a possible involvement of 
      PI3-kinase in the activation of the MAP kinase by insulin.
PG  - 735-41
AB  - Mitogen-activated protein (MAP) kinase plays crucial roles in cell growth and 
      differentiation. It has recently been shown that the MAP kinase cascade in growth 
      factor signaling diverges and cross-talks with other signaling pathways. In the 
      present study, we examined the effects of wortmannin, a specific inhibitor of 
      phosphatidylinositol 3-kinase (PI3-kinase), on the activation of Ras, Raf-1 
      kinase, and MAP kinase by insulin and epidermal growth factor (EGF). The effect 
      of LY294002, a structurally distinct PI3-kinase inhibitor, on the activation of 
      Raf-1 kinase by both ligands was also examined. In 3T3-L1 adipocytes, 25 nmol/l 
      wortmannin inhibited the insulin-induced activation of Raf-1 kinase to the basal 
      level, whereas the same dose of wortmannin had little effect on the EGF-induced 
      activation of Raf-1 kinase. One hundred micromol/l LY294002 blocked 
      insulin-induced activation of Raf-1 kinase without affecting EGF-induced 
      activation of this kinase. Twenty-five nmol/l wortmannin inhibited the 
      insulin-induced activation of MAP kinase to the basal level with no effect on the 
      EGF-induced activation of this kinase. But the same dose of wortmannin did not 
      affect the formation of guanosine 5'-triphosphate (GTP)-bound Ras stimulated by 
      either ligand. In KB cells, results similar to those in 3T3-L1 adipocytes were 
      obtained. In contrast, in Chinese hamster ovary cells overexpressing the human 
      insulin receptor (CHO-HIR cells), neither wortmannin nor LY294002 inhibited the 
      insulin-induced activation of Raf-1 kinase, and wortmannin had little effect on 
      the activation of MAP kinase by insulin. These results indicate that 1) 
      PI3-kinase or wortmannin-sensitive molecules are involved in the interaction 
      between activated Ras and Raf-1 kinase in the insulin signaling in 3T3-L1 
      adipocytes, 2) the involvement of PI3-kinase or wortmannin-sensitive molecules in 
      the insulin-induced activation of MAP kinase appears to be cell-type specific, 
      and 3) differential mechanisms to activate Raf-1 kinase and MAP kinase by insulin 
      and EGF exist.
FAU - Suga, J
AU  - Suga J
AD  - Department of Medicine and Clinical Science, Kyoto University Graduate School of 
      Medicine, Japan.
FAU - Yoshimasa, Y
AU  - Yoshimasa Y
FAU - Yamada, K
AU  - Yamada K
FAU - Yamamoto, Y
AU  - Yamamoto Y
FAU - Inoue, G
AU  - Inoue G
FAU - Okamoto, M
AU  - Okamoto M
FAU - Hayashi, T
AU  - Hayashi T
FAU - Shigemoto, M
AU  - Shigemoto M
FAU - Kosaki, A
AU  - Kosaki A
FAU - Kuzuya, H
AU  - Kuzuya H
FAU - Nakao, K
AU  - Nakao K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Androstadienes)
RN  - 0 (Chromones)
RN  - 0 (Insulin)
RN  - 0 (Morpholines)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-raf)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - 3T3 Cells
MH  - Adipocytes/drug effects/*enzymology
MH  - Androstadienes/pharmacology
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors/*metabolism
MH  - Chromones/pharmacology
MH  - Cricetinae
MH  - Enzyme Activation/drug effects
MH  - Epidermal Growth Factor/*pharmacology
MH  - Humans
MH  - Insulin/*pharmacology
MH  - Mice
MH  - Morpholines/pharmacology
MH  - Phosphatidylinositol 3-Kinases
MH  - Phosphotransferases (Alcohol Group Acceptor)/antagonists & inhibitors/*metabolism
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-raf
MH  - Wortmannin
EDAT- 1997/05/01 00:00
MHDA- 1997/05/01 00:01
CRDT- 1997/05/01 00:00
PHST- 1997/05/01 00:00 [pubmed]
PHST- 1997/05/01 00:01 [medline]
PHST- 1997/05/01 00:00 [entrez]
AID - 10.2337/diab.46.5.735 [doi]
PST - ppublish
SO  - Diabetes. 1997 May;46(5):735-41. doi: 10.2337/diab.46.5.735.