The Src-family kinase Lck can induce STAT3 phosphorylation and DNA binding activity.
Constitutive activation of the Src-family kinase Lck has been shown to lead to transformation. Constitutive activation of the STAT pathway of transcription factors has also been shown to be involved in transformation. An oncogenic form of the prototypical member of the Src-family, v-Src, has been shown to activate STAT3, and this activation is required for v-Src's transforming ability. To investigate whether Lck could directly activate STAT3, a baculovirus expression system was utilised. When Lck and STAT3 were coexpressed, STAT3 was found to have enhanced tyrosine phosphorylation and DNA binding activity. This finding was confirmed with experiments where exogenous Lck was added to baculovirus produced STAT3. Moreover, the activation of STAT3 by exogenous Lck could be attenuated by the Lck-specific inhibitor PP1. In addition, mammalian cells stably expressing a constitutively activated form of Lck were shown to have activated STAT3. These data provide strong evidence that, like v-Src, Lck can also directly activate STAT3, which contributes to the transformation process.
Lund
T C
TC
Department of Medical Microbiology and Immunology, Institute for Biomolecular Science, University of South Florida, Tampa 33612-4799, USA.
Coleman
C
C
Horvath
E
E
Sefton
B M
BM
Jove
R
R
Medveczky
M M
MM
Medveczky
P G
PG
D000818:Animals; D016367:Baculoviridae; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression; D005982:Glutathione Transferase / Q000235:genetics; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D011485:Protein Binding; D011506:Proteins / Q000494:pharmacology; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor; D018411:Spodoptera / Q000166:cytology; D013601:T-Lymphocytes / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D011506:Proteins; D011993:Recombinant Fusion Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C494088:Stat3 protein, rat; D015534:Trans-Activators; C073882:phosphoprotein phosphatase inhibitor 1; D014443:Tyrosine; D004247:DNA; D005982:Glutathione Transferase; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)