Involvement of nectin in inactivation of integrin αvβ3 after the establishment of cell-cell adhesion
Involvement of nectin in inactivation of integrin αvβ3 after the establishment of cell-cell adhesion
复制标题
DOI：
10.1074/jbc.m704195200
复制
发表时间：
2008-01-04
影响因子：
4.8
通讯作者：
Takai, Yoshimi
中科院分区：
文献类型：
--
作者：
Sakamoto, Yasuhisa;Ogita, Hisakazu;Takai, Yoshimi
整合素在细胞-基质连接的形成中起着至关重要的作用，也参与细胞的基本功能。在细胞-细胞连接的形成过程中，一种免疫球蛋白样细胞-细胞粘附分子连接素最初相互作用，并与另一种细胞-细胞粘附分子钙粘蛋白协同促进粘附连接（AJs）的形成。整合素α (v) β(3)的激活对于这种连接素诱导的AJs形成至关重要。然而，在AJs建立后，整合素α (v) β(3)变得无活性，并在AJs上保留与连接素的关联。整合素α (v) β(3)在AJs形成过程中的动态调控的分子机制尚不清楚。我们在这里发现，在Madin-Darby犬肾细胞中，参与整合素激活调控的磷脂酰肌醇-磷酸激酶I型γ 90 （PIPKI γ 90）的表达优先逆转了整合素α (v) β(3)在细胞-细胞粘附位点的失活，并部分破坏了基于e -钙粘蛋白的AJs。PIPKI γ的激活与其磷酸化状态相关。酪氨酸磷酸酶蛋白-酪氨酸磷酸酶mu （PTP mu）通过阻断整合素α (v) β(3)与talin的相互作用，有效地使PIPKI γ去磷酸化，从而取消PIPKI γ依赖性的整合素α (v) β(3)的激活。此外，PTP mu与连接素相关，其磷酸酶活性通过连接素的反式相互作用增强，导致PIPKI γ - 90磷酸化降低。因此，连接素的反式相互作用本质上是通过PTP mu诱导的PIPKI γ的失活，在AJs中失活整合素。
Integrin plays an essential role in the formation of cell-matrix junctions and is also involved in the fundamental cellular functions. In the process of the formation of cell-cell junctions, an immunoglobulin-like cell-cell adhesion molecule nectin initially trans-interacts together and promotes the formation of adherens junctions (AJs) cooperatively with another cell-cell adhesion molecule cadherin. The activation of integrin alpha(v)beta(3) is critically necessary for this nectin-induced formation of AJs. However, after the establishment of AJs, integrin alpha(v)beta(3) becomes inactive and retains the association with nectin at AJs. The molecular mechanism of this dynamic regulation of integrin alpha(v)beta(3) during the formation of AJs remains unclear. We found here that the expression of phosphatidylinositol-phosphate kinase type I gamma 90 (PIPKI gamma 90), which is involved in the regulation of integrin activation, in Madin-Darby canine kidney cells, preferentially reversed the inactivation of integrin alpha(v)beta(3) at cell-cell adhesion sites and partially disrupted E-cadherin-based AJs. The activation of PIPKI gamma is correlated with its phosphorylation state. The tyrosine phosphatase protein-tyrosine phosphatase mu (PTP mu) effectively dephosphorylated PIPKI gamma and thus canceled the PIPKI gamma-dependent activation of integrin alpha(v)beta(3) by blocking the interaction of integrin alpha(v)beta(3) with talin. Moreover, PTP mu associated with nectin, and its phosphatase activity was enhanced by the trans-interaction of nectin, leading to the decrease in PIPKI gamma 90 phosphorylation. Therefore, the trans-interaction of nectin essentially functions in the inactivation of integrin at AJs through the PTP mu-induced inactivation of PIPKI gamma.