ErbB-2 Activates Stat3α in a Src- and JAK2-dependent Manner

摘要: Stats (signal transducer and activator of transcription) are latent transcription factors that translocate from the cytoplasm to nucleus. Constitutive activation Stat3 alpha by upstream oncoproteins receptor tyrosine kinases has been found in many human tumors tumor-derived cell lines. Constitutively activated is often correlated with ErbB-2, a member EGFR family. To explore involvement ErbB-2 mechanism underlying this event, an point mutant was used as model constitutively receptor. Phenylalanine mutations (Y-->F) were made autophosphorylation sites receptor, their ability activate evaluated. Our results suggest JAK2 associates prior phosphorylation full requires participation other non-receptor kinases. Both Src Jak2 contribute but binds only when phosphorylated. also 1139 may be important for homology 2 domain association because lacking reduces bind significantly decreases its alpha.