Receptors for interleukin-3 (IL-3) and growth hormone mediate an IL-6-type transcriptional induction in the presence of JAK2 or STAT3.
To determine the specificity of signal transducer and activator of transcription (STAT) protein activation by box 3 motif-deficient hematopoietin receptors, expression vectors encoding the receptors for growth hormone, interleukin-3 (IL-3), and IL-4 were transiently transfected into COS-1 cells, together with expression vectors for Janus kinases (JAKs) and STAT proteins. Each receptor mediated a dose-dependent activation of STAT1 and STAT3, and for IL-3R and GHR this process was enhanced by JAK2. The data suggest that a box 3 motif in the cytoplasmic domain of the signal-transducing receptor to the JAK/STAT pathway. Transfection of the receptors, in combination with STAT3, into HepG2 cells reconstituted a cytokine-dependent stimulation of gene transcription through IL-6 response elements, providing evidence for a functional role of STAT3 in controlling gene expression.
Wang
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Y
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Morella
K K
KK
Ripperger
J
J
Lai
C F
CF
Gearing
D P
DP
Fey
G H
GH
Campos
S P
SP
Baumann
H
H
D000818:Animals; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004789:Enzyme Activation; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D053614:Janus Kinase 2; D007700:Kinetics; D008113:Liver Neoplasms; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D016184:Receptors, Colony-Stimulating Factor / Q000502:physiology; D018123:Receptors, Interleukin / Q000187:drug effects / Q000502:physiology; D016185:Receptors, Interleukin-3 / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D019948:Receptors, Interleukin-4; D011986:Receptors, Somatotropin / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D014407:Tumor Cells, Cultured
D016207:Cytokines; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D011518:Proto-Oncogene Proteins; D016184:Receptors, Colony-Stimulating Factor; D018123:Receptors, Interleukin; D016185:Receptors, Interleukin-3; D019948:Receptors, Interleukin-4; D011986:Receptors, Somatotropin; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2