Lee M M, Fink B D, Grunwald G B
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Dev Genet. 1997;20(3):224-34. doi: 10.1002/(SICI)1520-6408(1997)20:3<224::AID-DVG5>3.0.CO;2-9.
N-cadherin, a member of the cadherin family of calcium-dependent cell adhesion molecules, mediates adhesive and signaling interactions between cells during development. N-Cadherin undergoes dynamic spatiotemporal changes in expression which correlate with morphogenetic movements of cells during organogenesis and histogenesis. We have previously shown that N-cadherin expression during development is regulated by several mechanisms, including mRNA expression, cytokine modulation, and proteolytically mediated turnover, yielding the NCAD90 protein. The present study was directed at determining the extent to which N-cadherin in primary embryonic cells is the target of endogenous kinases and phosphatases, as well as the effects of modulation of these enzymes on NCAD90 expression. The results of phosphoamino acid analyses, peptide mapping, and measurements of N-cadherin and NCAD90 expression in embryonic tissues indicate that N-cadherin is indeed the target of endogenous kinase and phosphatase action, and that modulation of different classes of these enzymes can result in either stimulation or inhibition of NCAD90 production. These results provide a mechanistic explanation for observations that cadherin function is downregulated following expression of exogenously introduced viral tyrosine kinases and provide a function for the tyrosine phosphatases recently found in association with cadherins. The results indicate that N-cadherin expression during retinal development is possibly regulated in part by modulation of its phosphorylation state, the balance of which may determine whether N-cadherin remains stably expressed or is targeted for proteolytically mediated turnover to produce NCAD90.
N-钙黏蛋白是钙依赖性细胞黏附分子钙黏蛋白家族的成员之一，在发育过程中介导细胞间的黏附及信号相互作用。N-钙黏蛋白的表达呈现动态时空变化，这与器官发生和组织发生过程中细胞的形态发生运动相关。我们之前已经表明，发育过程中N-钙黏蛋白的表达受多种机制调控，包括mRNA表达、细胞因子调节以及蛋白水解介导的周转，从而产生NCAD90蛋白。本研究旨在确定原代胚胎细胞中的N-钙黏蛋白在多大程度上是内源性激酶和磷酸酶的作用靶点，以及这些酶的调节对NCAD90表达的影响。磷酸氨基酸分析、肽图谱分析以及胚胎组织中N-钙黏蛋白和NCAD90表达测量的结果表明，N-钙黏蛋白确实是内源性激酶和磷酸酶作用的靶点，并且这些酶不同类别的调节可导致NCAD90产生的刺激或抑制。这些结果为以下观察提供了机制解释：在外源引入的病毒酪氨酸激酶表达后，钙黏蛋白功能下调，并且为最近发现的与钙黏蛋白相关的酪氨酸磷酸酶提供了一种功能。结果表明，视网膜发育过程中N-钙黏蛋白的表达可能部分受其磷酸化状态调节，其平衡可能决定N-钙黏蛋白是保持稳定表达还是成为蛋白水解介导周转的靶点以产生NCAD90。
