Smad2 transduces common signals from receptor serine-threonine and tyrosine kinases.
SMAD proteins mediate signals from receptor serine-threonine kinases (RSKs) of the TGF-beta superfamily. We demonstrate here that HGF and EGF, which signal through RTKs, can also mediate SMAD-dependent reporter gene activation and induce rapid phosphorylation of endogenous SMAD proteins by kinase(s) downstream of MEK1. HGF induces phosphorylation and nuclear translocation of epitope-tagged Smad2 and a mutation that blocks TGF-beta signaling also blocks HGF signal transduction. Smad2 may thus act as a common positive effector of TGF-beta- and HGF-induced signals and serve to modulate cross talk between RTK and RSK signaling pathways.
de Caestecker
M P
MP
Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-5055 USA.
Parks
W T
WT
Frank
C J
CJ
Castagnino
P
P
Bottaro
D P
DP
Roberts
A B
AB
Lechleider
R J
RJ
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D016147:Genes, Tumor Suppressor; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D018125:Receptors, Transforming Growth Factor beta / Q000819:agonists / Q000502:physiology*; D015398:Signal Transduction; D051899:Smad2 Protein; D015534:Trans-Activators; D015533:Transcriptional Activation; D014162:Transfection
D004268:DNA-Binding Proteins; D018125:Receptors, Transforming Growth Factor beta; D051899:Smad2 Protein; D015534:Trans-Activators; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases