Publication Date:
1999-12-30
Description:
Expression of Q205L Galphao (Galphao*), an alpha subunit of heterotrimeric guanine nucleotide-binding proteins (G proteins) that lacks guanosine triphosphatase (GTPase) activity in NIH-3T3 cells, results in transformation. Expression of Galphao* in NIH-3T3 cells activated signal transducer and activator of transcription 3 (Stat3) but not mitogen-activated protein (MAP) kinases 1 or 2. Coexpression of dominant negative Stat3 inhibited Galphao*-induced transformation of NIH-3T3 cells and activation of endogenous Stat3. Furthermore, Galphao* expression increased activity of the tyrosine kinase c-Src, and the Galphao*-induced activation of Stat3 was blocked by expression of Csk (carboxyl-terminal Src kinase), which inactivates c-Src. The results indicate that Stat3 can function as a downstream effector for Galphao* and mediate its biological effects.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ram, P T -- Horvath, C M -- Iyengar, R -- 1F32 CA79134-01/CA/NCI NIH HHS/ -- DK-38671/DK/NIDDK NIH HHS/ -- GM-54508/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2000 Jan 7;287(5450):142-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Immunobiology Center, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA. ramp01@doc.mssm.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10615050" target="_blank"〉PubMed〈/a〉
Keywords:
3T3 Cells
;
Animals
;
Cell Line, Transformed
;
*Cell Transformation, Neoplastic
;
DNA-Binding Proteins/*metabolism
;
Enzyme Activation
;
GTP-Binding Protein alpha Subunits
;
Genes, Reporter
;
Heterotrimeric GTP-Binding Proteins/genetics/*metabolism
;
MAP Kinase Signaling System
;
Mice
;
Mitogen-Activated Protein Kinase 1/metabolism
;
Mitogen-Activated Protein Kinases/metabolism
;
Neurites/physiology
;
Neuronal Plasticity
;
Neurons/metabolism/physiology
;
Phosphorylation
;
Phosphotyrosine/metabolism
;
Protein-Tyrosine Kinases/metabolism
;
STAT3 Transcription Factor
;
Signal Transduction
;
Trans-Activators/*metabolism
;
Transfection
;
src-Family Kinases
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
