The role of Protein Kinase Cd in Hepatocyte Growth Factor-induced cell motility

• Main Authors: Chien-Lin Chen, 陳建霖
• Other Authors: Hong-Chen Chen
• Format: Others
• Language: zh-TW
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/04021132118228366343

碩士 === 國立中興大學 === 生命科學系 === 93 === Protein Kinase C (PKC), a novel type of PKC, has been shown to play critical roles in the control of cell behavior such as cell proliferation, differentiation, and apoptosis. However, its role in hepatocyte growth factor (HGF)-elicited cell functions has not been reported. In this study, we found that the specific PKCinhibitor rottlerin abrogated HGF-induced scatter of Madin-Darby canine kidney cells. Small interfering RNA-mediated knockdown of PKC inhibited Madin-Darby canine kidney cells motility. Overexpression of PKC in MDCK cells promoted cell motility. In contrast, the kinase-dead mutant suppresses cell migration. Moreover, whereas phorbol ester stimulated a transient activation of PKC, HGF induced a delayed but sustained activation of PKC whose activity was increased 3 h after HGF treatment, gradually reached a plateau (10-fold increase) at 12 h, and lasted for at least another 12 h. Expression of green fluorescent protein tagged PKC in Madin-Darby canine kidney cells revealed that PKC was localized throughout the cytoplasm. Upon HGF stimulation, PKC-GFP became evident at polarized Golgi complexes and lamellipodia. Overexpression of the C1B domain deletion mutant of PKC in MDCK cells partially inhibited HGF-elicited PKCkinase activity and cell motility. Taken together, our results establish a new role for PKC in HGF signaling and implicate its role in cell motility.