Minimal mutation of the cytoplasmic tail inhibits the ability of E-cadherin to activate Rac but not phosphatidylinositol 3-kinase - Direct evidence of a role for cadherin-activated Rac signaling in adhesion and contact formation
Minimal mutation of the cytoplasmic tail inhibits the ability of E-cadherin to activate Rac but not phosphatidylinositol 3-kinase - Direct evidence of a role for cadherin-activated Rac signaling in adhesion and contact formation
复制标题
DOI：
10.1074/jbc.m213171200
复制
发表时间：
2003-06-06
影响因子：
4.8
通讯作者：
Yap, AS
中科院分区：
文献类型：
--
作者：
Goodwin, M;Kovacs, EM;Yap, AS
经典的钙粘蛋白是粘附激活的细胞信号受体。特别是，嗜同性钙粘蛋白连接可以直接激活Rho家族GTP酶和磷脂酰肌醇3-激酶（PI 3-激酶），这些信号分子具有支持这些粘附分子在发育和疾病期间的形态发生作用的能力。然而，钙粘蛋白信号转导的分子基础尚未阐明，其对钙粘蛋白功能的确切贡献也尚未了解。一个有吸引力的假设是钙粘蛋白激活的信号传导参与稳定粘附接触（雅普，A.美国，和Kovacs，E. M.等人（2003）J. Cell Biol.160，11-16）。我们现在报告，最小的突变的钙粘蛋白的胞质尾部解偶联结合p120-ctn消融的能力，E-钙粘蛋白激活Rac。这伴随着细胞建立稳定的粘附接触能力的严重缺陷，这些缺陷被持续的Rac信号所挽救。这些数据提供了直接的证据，钙粘蛋白激活的Rac信号在接触形成和粘合剂稳定的作用。与此相反，钙粘蛋白激活的PI 3-激酶信号不受p120-ctn结合的损失。因此，E-cadherin激活Rac信号传导的分子要求与刺激PI 3-激酶的分子要求不同，我们推测p120-ctn可能在E-cadherin-Rac信号传导通路中发挥核心作用。
Classic cadherins are adhesion-activated cell signaling receptors. In particular, homophilic cadherin ligation can directly activate Rho family GTPases and phosphatidylinositol 3-kinase (PI3-kinase), signaling molecules with the capacity to support the morphogenetic effects of these adhesion molecules during development and disease. However, the molecular basis for cadherin signaling has not been elucidated, nor is its precise contribution to cadherin function yet understood. One attractive hypothesis is that cadherin-activated signaling participates in stabilizing adhesive contacts ( Yap, A. S., and Kovacs, E. M. ( 2003) J. Cell Biol. 160, 11-16). We now report that minimal mutation of the cadherin cytoplasmic tail to uncouple binding of p120-ctn ablated the ability of E-cadherin to activate Rac. This was accompanied by profound defects in the capacity of cells to establish stable adhesive contacts, defects that were rescued by sustained Rac signaling. These data provide direct evidence for a role of cadherin-activated Rac signaling in contact formation and adhesive stabilization. In contrast, cadherin-activated PI3-kinase signaling was not affected by loss of p120-ctn binding. The molecular requirements for E-cadherin to activate Rac signaling thus appear distinct from those that stimulate PI3-kinase, and we postulate that p120-ctn may play a central role in the E-cadherin-Rac signaling pathway.