Du X, Saido T C, Tsubuki S, Indig F E, Williams M J, Ginsberg M H
Department of Vascular Biology, Scripps Research Institute, La Jolla, California 92037, USA.
J Biol Chem. 1995 Nov 3;270(44):26146-51. doi: 10.1074/jbc.270.44.26146.
The cytoplasmic domains of integrin beta subunits are involved in bidirectional transmembrane signaling. We report that the cytoplasmic domain of the integrin beta 3 subunit undergoes limited proteolysis by calpain, an intracellular calcium-dependent protease. Calpain cleavage occurs during platelet aggregation induced by agonists such as thrombin. Five cleavage sites have been identified. Four of these sites (C-terminal to Thr741, Tyr747, Phe754, and Tyr759) are utilized in intact platelets and flank two NXXY motifs (Asn744-Pro-Leu-Tyr747 and Asn756-Ile-Thr-Tyr759). The fifth site (Ala735) is accessible to calpain after EDTA treatment of the alpha IIb beta 3 heterodimer. The NXXY motif is critical to the bidirectional signaling functions of beta 3 integrins and their association with the cytoskeleton. Thus, calpain cleavage of the beta 3 cytoplasmic domain may provide a means to regulate integrin signaling functions.
整合素β亚基的胞质结构域参与双向跨膜信号传导。我们报告称，整合素β3亚基的胞质结构域会被钙蛋白酶（一种细胞内钙依赖性蛋白酶）进行有限的蛋白水解。钙蛋白酶切割发生在凝血酶等激动剂诱导的血小板聚集过程中。已确定了五个切割位点。其中四个位点（在Thr741、Tyr747、Phe754和Tyr759的C末端）在完整血小板中被利用，并位于两个NXXY基序（Asn744-Pro-Leu-Tyr747和Asn756-Ile-Thr-Tyr759）两侧。第五个位点（Ala735）在对αIIbβ3异二聚体进行EDTA处理后可被钙蛋白酶作用。NXXY基序对β3整合素的双向信号传导功能及其与细胞骨架的关联至关重要。因此，β3胞质结构域的钙蛋白酶切割可能提供一种调节整合素信号传导功能的方式。
