Dj. Meyer et al., GROWTH-HORMONE INDUCES A DNA-BINDING FACTOR-RELATED TO THE INTERFERON-STIMULATED 91-KDA TRANSCRIPTION FACTOR, The Journal of biological chemistry, 269(7), 1994, pp. 4701-4704
Signaling mechanisms leading to regulation of gene transcription by gr
owth hormone (GH) and other molecules that signal via the cytokine rec
eptor family have been elusive. Based upon recent findings that GH and
interferons activate JAK family tyrosine kinases, we have identified
a novel signaling pathway leading from the GH receptor to the nucleus.
We report that in 3T3-F442A fibroblasts, GH stimulates tyrosyl phosph
orylation of a protein recognized by antibody to p91, a component of D
NA-binding complexes that are activated by tyrosyl phosphorylation in
response to interferons alpha and gamma. In addition, a GH-inducible D
NA binding factor (GHIF) is identified that binds to the c-sis-inducib
le element of the c-fos promoter. GHIF contains a protein antigenicall
y related to p91 and is tyrosyl-phosphorylated. These findings indicat
e that in signaling between their receptors and the nucleus, GH and in
terferons utilize related or identical components, including JAK famil
y tyrosine kinases and proteins in the p91 family. When combined with
recent findings that many members of the cytokine receptor family acti
vate JAK kinases, including some cytokines that activate p91-related p
roteins, these findings suggest that signaling pathways involving JAB
kinases and p91 family members may be broadly distributed.