| Summary: | 碩士 === 國立中興大學 === 生物醫學研究所 === 93 === Focal adhesion kinase (FAK) is an important mediator of signal transduction pathways initiated by integrins in cell migration, survival and cell cycle regulation. The Src family of cytosolic protein tyrosine kinases function intimately with FAK in integrin signaling pathways. Furthermore, the original identification of FAK as a protein with increased tyrosine phosphorylation in v-Src-transformed cells suggests that FAK may mediate some of the oncogenic functions of Src. The Tyr-397 is the major autophosphorylation site of FAK that serves as a binding site for the SH2 domain of Src. In fact, the association of FAK with Src has been demonstrated in a number of in vivo and in vitro systems. In this thesis, I have studied the effect of the expression of FAK Y397F mutant on v-Src-stimulated cell transformation by utilizing a tetracycline repression system established in FAK-null mouse embryo fibroblasts. I found the FAK Y397F mutant appeared to play dual roles in v-Src-stimulated cell transformation, which promoted v-Src-stimulated matrigel invasion but inhibited the v-Src-stimulated anchorage-independent cell growth. When the cells were adherent on culture dishes, v-Src efficiently phosphorylated FAK Y397F mutant, concomitant with increased phosphorylation of AKT, ERK, and JNK and increased expression of matrix metalloproteinase 2. In contrast, when the cells were grown in suspension, v-Src failed to phosphorylate FAK Y397F mutant and activate AKT, ERK, and JNK. This inhibitory effect of FAK Y397F mutant on v-Src-stimulated signaling may explain its suppressive role in the v-Src-stimulated anchorage independent cell growth.
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