ErbB receptor-induced activation of stat transcription factors is mediated by Src tyrosine kinases.

摘要: Epidermal growth factor (EGF) binding to its receptor, ErbB1, triggers various signal transduction pathways, one of which leads the activation transducer and activator transcription (Stat) factors. The mechanism underlying ErbB1-induced Stat whether Stats are downstream targets other ErbB receptors have not been explored. In this report we show that ErbB2, ErbB3, ErbB4 do potentiate Stat5 phosphorylation by EGF. However, neu differentiation factor-induced heterodimers ErbB2 activated Stat5. A431 cells, Stat1, Stat3, Stat5, were constitutively complexed with ErbB1 rapidly phosphorylated on tyrosine in response Neither mutation conserved residue (Tyr694) nor inactivation Stat5a SH2 domain disrupted association. an intact was necessary for EGF-induced phosphorylation. contrast prolactin, induced only Tyr694 Stat5a, EGF promoted additional residue(s). Janus kinases (Jaks) also associated EGF-related ligands. provide evidence EGF- dependent Src but Jak kinases. Upon stimulation, c-Src recruited Stat/ErbB receptor complexes. Pharmacological kinase inhibitors a dominant negative ablated both Jaks did affect Taken together, experiments establish two independent roles kinases: (i) key molecules receptor-mediated signaling (ii) potential upstream regulators