PMID- 9388274
OWN - NLM
STAT- MEDLINE
DCOM- 19980108
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 272
IP  - 49
DP  - 1997 Dec 5
TI  - Heat shock activates c-Src tyrosine kinases and phosphatidylinositol 3-kinase in 
      NIH3T3 fibroblasts.
PG  - 31196-202
AB  - There is increasing evidence that cellular responses to stress are in part 
      regulated by protein kinases, although specific mechanisms are not well defined. 
      The purpose of these experiments was to investigate potential upstream signaling 
      events activated during heat shock in NIH3T3 fibroblasts. Experiments were 
      designed to ask whether heat shock activates p60 c-Src tyrosine kinase or 
      phosphatidylinositol 3-kinase (PI 3-kinase). Using in vitro protein kinase 
      activity assays, it was demonstrated that heat shock stimulates c-Src and PI 
      3-kinase activity in a time-dependent manner. Also, there was increased PI 
      3-kinase activity in anti-phosphotyrosine and anti-c-Src immunoprecipitated 
      immunocomplexes from heated cells. Heat shock activated mitogen-activated protein 
      kinase (MAPK) and p70 S6 kinase (S6K) in these cells. The role of PI 3-kinase in 
      regulating heat shock activation of MAPK and p70 S6K was investigated using 
      wortmannin, a specific pharmacological inhibitor of PI 3-kinase. The results 
      demonstrated that wortmannin inhibited heat shock activation of p70 S6K but only 
      partially inhibited heat activation of MAPK. A dominant negative Raf mutant 
      inhibited activation of MAPK by heat shock but did not inhibit heat shock 
      stimulation of p70 S6K. Genistein, a tyrosine kinase inhibitor, and suramin, a 
      growth factor receptor inhibitor, both inhibited heat shock stimulation of MAPK 
      activity and tyrosine phosphorylation of MAPK. Furthermore, a selective epidermal 
      growth factor receptor (EGFR) inhibitor, tryphostin AG1478, and a dominant 
      negative EGFR mutant also inhibited heat shock activation of MAPK. Heat shock 
      induced EGFR phosphorylation. These results suggest that early upstream signaling 
      events in response to heat stress may involve activation of PI 3-kinase and 
      tyrosine kinases, such as c-Src, and a growth factor receptor, such as EGFR; 
      activation of important downstream pathways, such as MAPK and p70 S6K, occur by 
      divergent signaling mechanisms similar to growth factor stimulation.
FAU - Lin, R Z
AU  - Lin RZ
AD  - Veterans Affairs Palo Alto Health Care System and Geriatrics Research, Education 
      and Clinical Center, Palo Alto, California 94304, USA.
FAU - Hu, Z W
AU  - Hu ZW
FAU - Chin, J H
AU  - Chin JH
FAU - Hoffman, B B
AU  - Hoffman BB
LA  - eng
GR  - HL41315/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Androstadienes)
RN  - 0 (Enzyme Inhibitors)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - 3T3 Cells
MH  - Androstadienes/administration & dosage/pharmacology
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/administration & dosage/pharmacology
MH  - ErbB Receptors/metabolism
MH  - Fibroblasts/enzymology
MH  - *Hot Temperature
MH  - Mice
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Ribosomal Protein S6 Kinases/antagonists & inhibitors/*metabolism
MH  - Signal Transduction
MH  - Wortmannin
EDAT- 1998/01/10 00:00
MHDA- 1998/01/10 00:01
CRDT- 1998/01/10 00:00
PHST- 1998/01/10 00:00 [pubmed]
PHST- 1998/01/10 00:01 [medline]
PHST- 1998/01/10 00:00 [entrez]
AID - S0021-9258(19)89667-9 [pii]
AID - 10.1074/jbc.272.49.31196 [doi]
PST - ppublish
SO  - J Biol Chem. 1997 Dec 5;272(49):31196-202. doi: 10.1074/jbc.272.49.31196.