Mechanisms of STAT Protein Activation by Oncogenic KIT Mutants in Neoplastic Mast Cells

摘要: Mutations in the c-kit gene occur vast majority of mastocytosis. In adult patients as well cell line derived from mast neoplasms, mutations almost exclusively at amino acid 816 within kinase domain KIT. Among downstream effectors KIT signaling, STAT3 and STAT5 have been shown to be critical for proliferation elicited by KIT-Asp816 mutant protein. However, little is known about mechanisms activation STAT proteins. this study, we identify clarify contribution various kinases two widely used neoplastic lines, P815 HMC-1. We show that STAT1, -3, -5 proteins are activated mutant. All three located nucleus phosphorylated on serine residues. can directly phosphorylate STATs activation-specific tyrosine residues vitro. cells, SRC family JAKs diversely contribute phosphorylation Using a panel inhibitors, provide evidence implication or exclusion serine/threonine responsible lines. Finally, only transcriptionally active these cells. This suggests STAT1 independent their transcription factor function.