PROTEIN-TYROSINE PHOSPHORYLATION AS A MECHANISM WHICH REGULATES CYTOKINE ACTIVATION OF EARLY RESPONSE GENES

Two well-defined rapid responses which occur as a consequence of growth factors binding to their cell surface receptors involve tyrosine phosphorylation of cellular proteins and the induction of the transcription of cellular genes. Recent advances have been made in purification and cloning of Src homology 2 and 3 (SH2/SH3) domain-containing transcription factors which are required for the activation of early response genes by interferons. These transcription factors are covalently modified by tyrosine phosphorylation such that they interact with enhancers needed for interferon-stimulated gene expression. The Jak family of tyrosine kinases are also an integral component in these signalling cascades. The information gained concerning interferon signalling has now been extended to include a broad network of cytokine-regulated signalling systems which use tyrosine phosphorylation of a family of structurally related proteins to activate transcription of early response genes.