Kaufman David A, Albelda Steven M, Sun Jing, Davies Peter F
Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, USA.
Biochem Biophys Res Commun. 2004 Aug 6;320(4):1076-81. doi: 10.1016/j.bbrc.2004.06.055.
Phosphorylation of tyrosine residues on platelet-endothelial cell adhesion molecule-1 (PECAM-1), followed by signal transduction events, has been described in endothelial cells following exposure to hyperosmotic and fluid shear stress. However, it is unclear whether PECAM-1 functions as a primary mechanosensor in this process. Utilizing a PECAM-1-null EC-like cell line, we examined the importance of cellular localization and the extracellular and transmembrane domains in PECAM-1 phosphorylation responses to mechanical stress. Tyrosine phosphorylation of PECAM-1 was stimulated in response to mechanical stress in null cells transfected either with full length PECAM-1 or with PECAM-1 mutants that do not localize to the lateral cell-cell adhesion site and that do not support homophilic binding between PECAM-1 molecules. Furthermore, null cells transfected with a construct that contains the intact cytoplasmic domain of PECAM-1 fused to the extracellular and transmembrane domains of the interleukin-2 receptor also underwent mechanical stress-induced PECAM-1 tyrosine phosphorylation. These findings suggest that mechanosensitive PECAM-1 may lie downstream of a primary mechanosensor that activates a tyrosine kinase.
血小板内皮细胞黏附分子-1（PECAM-1）酪氨酸残基的磷酸化，随后发生信号转导事件，已在暴露于高渗和流体剪切应力后的内皮细胞中有所描述。然而，尚不清楚PECAM-1在此过程中是否作为主要的机械传感器发挥作用。利用一种缺乏PECAM-1的类内皮细胞系，我们研究了细胞定位以及细胞外和跨膜结构域在PECAM-1对机械应力的磷酸化反应中的重要性。在用全长PECAM-1或不定位到细胞间侧向黏附位点且不支持PECAM-1分子间同源性结合的PECAM-1突变体转染的缺失细胞中，机械应力刺激了PECAM-1的酪氨酸磷酸化。此外，用包含与白细胞介素-2受体的细胞外和跨膜结构域融合的PECAM-1完整胞质结构域的构建体转染的缺失细胞，也经历了机械应力诱导的PECAM-1酪氨酸磷酸化。这些发现表明，机械敏感的PECAM-1可能位于激活酪氨酸激酶的主要机械传感器的下游。
