Signaling Pathways of Cell Morphology and Adhesion.

本项目旨在通过国际合作研究，明确由sh2 -磷酸酪氨酸结合或sh3 -脯氨酸结合调节的蛋白-蛋白相互作用调控细胞形态和粘附的关键信号通路。近年来的研究进展表明，调控细胞形态和粘附的信号通路在细胞生长、分化、器官形成等生命必需过程中起着至关重要的作用。该项目的合作者Mayr和Hanafusa发现，由sh2 -磷酸酪氨酸结合或sh3 -脯氨酸结合调节的蛋白-蛋白相互作用在该信号通路中起关键作用。这个项目的负责人Hamaguchi表明，钙粘蛋白依赖的细胞粘附受到酪氨酸磷酸化的调节。在这些研究的基础上，Hamaguchi与Mayr和Hanafusa合作研究了调节cadherin功能的信号通路，发现c-ras在v-src和v-fps转化细胞的细胞-细胞粘附中起重要作用。此外，Hamaguchi发现c-ras在v-crk转化细胞的细胞粘附中也起着重要作用。目前，使用Mayr提供的GST-SH2融合蛋白对细胞粘附至关重要的酪氨酸磷酸化蛋白进行了进一步的研究。

This project is aimed to clarify the critical signaling pathway for the regulation of cell morphology and adhesion that depends on protein-protein interactions regulated by SH2-phosphotyrosine binding or SH3-proline bindings, under the international collaborative study. Advance of recent study revealed that signaling pathway that regulates cell morphology and adhesion plays a critical role in cell growth, differentiation, organ formation and others essential for life.Collaborators of this project, Mayr and Hanafusa have revealed that protein-protein interactions regulated by SH2-phosphotyrosine binding or SH3-proline bindings play a key role in this signaling pathway. The director of this project, Hamaguchi showed that cadherin-dependent cell adhesion was regulated by tyrosine phosphorylation. Based on these studies, Hamaguchi studied, in collaboration with Mayr and Hanafusa, the signaling pathway that regulate cadherin function, and found that c-ras playd an important role in cell-cell adhesion in v-src and v-fps transformed cells. In addition, Hamaguchi found that c-ras also playd an important role in cell-cell adhesion in v-crk transformed cells. Further studies of tyrosine phosphorylated proteins critical for cell adhesion are currently underwent by use of GST-SH2 fusion protein that offered by Mayr.