Department of Biochemistry and Microbiology, Institute of Chemical Technology, Prague, Technická 5, Prague 6, 166 28, Czech Republic.
Cell Signal. 2014 Jan;26(1):173-8. doi: 10.1016/j.cellsig.2013.09.020. Epub 2013 Oct 5.
Annexin A1 (ANXA1) is the first characterized member of the annexins superfamily. It binds the cellular membrane phospholipids in Ca(2+) regulated manner. Annexin A1 has been found in several tissues and many physiological roles as hormones secretion, vesiculation, inflammatory response, apoptosis and differentiation have been shown. Its subcellular localization and binding with many partner proteins are altered accordingly with its physiological role. The Annexin A1 membrane localization is crucial for binding to receptors, suggesting a paracrine and juxtacrine extracellular action. Annexin A1 is subjected to several post-translational modifications. In particular the protein is phosphorylated on several residues both on the N-terminal functional domain and on the C-terminus core. Different kinases have been identified as responsible for the phosphorylation status of selective residues. The specific change in the phosphorylation status on the different sites alters ANXA1 localization, binding properties and functions. This review shows the physiological relevance of the ANXA1 phosphorylation leading to the conclusion that numerous and different roles of Annexin A1 could be associated with different phosphorylations to alter not only intracellular localization and bindings to its partners but also the extracellular receptor interactions.
膜联蛋白 A1（ANXA1）是钙调节膜结合蛋白家族中第一个被鉴定的成员。它结合细胞膜磷脂。已在多种组织中发现 Annexin A1，并显示出许多生理作用，如激素分泌、小泡形成、炎症反应、细胞凋亡和分化。其亚细胞定位及其与许多伴侣蛋白的结合随其生理作用而改变。ANXA1 的膜定位对于与受体结合至关重要，这表明其具有旁分泌和细胞旁分泌的细胞外作用。膜联蛋白 A1 可发生多种翻译后修饰。特别是该蛋白在 N 端功能域和 C 端核心上的几个残基上发生磷酸化。已经鉴定出不同的激酶负责选择性残基的磷酸化状态。不同位点磷酸化状态的特定变化改变了 ANXA1 的定位、结合特性和功能。这篇综述展示了 ANXA1 磷酸化的生理相关性，得出的结论是，膜联蛋白 A1 的许多不同作用可能与不同的磷酸化有关，不仅可以改变其在细胞内的定位和与伴侣的结合，还可以改变其与细胞外受体的相互作用。
