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Science 287 (5450): 142-144

Copyright © 2000 by the American Association for the Advancement of Science

Stat3-Mediated Transformation of NIH-3T3 Cells by the Constitutively Active Q205L Galpha o Protein

Prahlad T. Ram, 1* Curt M. Horvath, 2 Ravi Iyengar 1

Expression of Q205L Galpha o (Galpha o*), 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 Galpha o* 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 Galpha o*-induced transformation of NIH-3T3 cells and activation of endogenous Stat3. Furthermore, Galpha o* expression increased activity of the tyrosine kinase c-Src, and the Galpha o*-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 Galpha o* and mediate its biological effects.

1 Department of Pharmacology,
2 Immunobiology Center, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.
*   To whom correspondence should be addressed. E-mail: ramp01{at}doc.mssm.edu


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