期刊
MOLECULAR AND CELLULAR BIOCHEMISTRY
卷 362, 期 1-2, 页码 65-70出版社
SPRINGER
DOI: 10.1007/s11010-011-1128-3
关键词
Pancreatic cancer; c-Src; Furin; PDGF-BB; MT1-MMP
类别
资金
- National Natural Science Foundation of PR China [30873033]
- Major State Basic Research Development Program [2009CB521800, 2010CB529400]
Furin is a member of the proprotein convertase family, which is capable of cleaving the precursors of a wide variety of substrates including membrane-type 1 matrix metalloproteinase (MT1-MMP) proenzyme. c-Src is activated by growth factors, and has been linked with a poor prognosis in pancreatic cancer (PCa). Both c-Src and Furin play crucial roles in tumorigenesis, and the mechanism controlling their association is not understood. Modulation of the association between Furin and pro-MT1-MMP by c-Src inhibitor PP2 was evaluated by western blotting, assay of in vitro enzyme, co-immunoprecipitation (co-IP), and confocal immunofluorescence microscopy. Human platelet-derived growth factor BB (PDGF-BB) activated c-Src and induced c-Src-dependent association of Furin with pro-MT1-MMP in HPAC pancreatic cancer cells. Co-IP and confocal immunofluorescence assays revealed that c-Src interacts with Furin in vivo. The SH2 domain appeared to be important for c-Src interaction with Furin. In addition, we showed that Furin protein is tyrosine phosphorylated. Association between Furin and MT1-MMP is regulated by the tyrosine kinase c-Src.
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