The non-receptor tyrosine kinase c-Src mediates the PDGF-induced association between Furin and pro-MT1-MMP in HPAC pancreatic cells.
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.
Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, China.
Chong
C
Shi
Yongchao
Y
Ma
Hao
H
Liu
Yuxiang
Y
Zhang
Zesheng
Z
Wang
Hongti
H
Jia
D000077214:Becaplermin; D000081247:CSK Tyrosine-Protein Kinase; D045744:Cell Line, Tumor; D045683:Furin / Q000378:metabolism*; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D019061:src-Family Kinases
C412373:AG 1879; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011743:Pyrimidines; C075278:platelet-derived growth factor A; D000077214:Becaplermin; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; D045683:Furin; D053511:Matrix Metalloproteinase 14