STAT3 activation by type I interferons is dependent on specific tyrosines located in the cytoplasmic domain of interferon receptor chain 2c. Activation of multiple STATS proceeds through the redundant usage of two tyrosine residues.

摘要: Abstract Human type I interferons (IFNs) play an important role in the regulation of antiviral defense mechanisms, immunomodulatory activities, and growth control. Recent efforts have demonstrated importance IFNs activation ofsignal transducers activators transcription (STATs). The STAT1 STAT2 IFN-dependent JAK-STAT signaling is well established; however, STAT3 its by remains unclear. Understanding increasing interest because recent studies that may a cancer. Studies revealed constitutively active number cancer cell lines overexpression form transforms normal fibroblasts. Therefore, exhibits properties indicative known oncogenes. In this report, we define IFN receptor identify for first time tyrosine residues present cytoplasmic domain IFNAR2c are critical activation. was measured human lung fibrosarcoma line lacking but stably expressing various mutants. We show here addition to phosphorylation STAT3, using STAT3-dependent electrophoretic mobility shift assay STAT3-specific reporter can also be demonstrated. Furthermore, demonstrate proceeds through novel mechanism dependent on two tyrosines, Tyr337 Tyr512, contained within conserved six-amino acid residue motif, GxGYxM. Surprisingly, both tyrosines were previously shown required Our results reveal activate multiple STATs via overlapping usage located IFNAR2c.