GROWTH-HORMONE INDUCES A DNA-BINDING FACTOR-RELATED TO THE INTERFERON-STIMULATED 91-KDA TRANSCRIPTION FACTOR

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.