Leukocyte integrins ¦ÁL¦Â2, ¦ÁM¦Â2 and ¦ÁX¦Â2 as collagen receptors¡ªReceptor activation and recognition of GFOGER motif
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- 作者：Matti Lahti ; matti.lahti@iki.fi ; mjlahti@utu.fi ; Jyrki Heino ; Jarmo Kä ; pylä
- 关键词：Adhesion ; Cell trafficking ; Collagen ; Complement receptors ; Extracellular matrix ; Integrin
- 刊名：The International Journal of Biochemistry and Cell Biology
- 出版年：2013
- 出版时间：July, 2013
- 年：2013
- 卷：45
- 期：7
- 页码：1204-1211
- 全文大小：1096 K
文摘
Integrins ¦ÁL¦Â2, ¦ÁM¦Â2 and ¦ÁX¦Â2 are expressed on leukocytes. Their primary ligands are counter transmembrane receptors or plasma proteins, such as intercellular cell adhesion molecule-1 (ICAM-1) or components of complement system (iC3b, iC4b), respectively. Function blocking antibodies for these integrins may also reduce cell adhesion to collagens. To make the first systematical comparison of human ¦ÁL¦Â2, ¦ÁM¦Â2 and ¦ÁX¦Â2 as collagen receptors, we produced the corresponding integrin ¦ÁI domains both in wild-type and activated form and measured their binding to collagens I-VI. In the ¡°closed¡± (wild-type) conformation, the ¦ÁLI and ¦ÁMI domains bound with low avidity to their primary ligands, and the interaction with collagens was also very weak. Gain-of-function mutations ¦ÁL I306G, ¦ÁL K287C/K294C and ¦ÁM I316G are considered to mimic ¡°open¡±, activated ¦ÁI domains. The binding of these activated ¦ÁI domains to the primary ligands was clearly stronger and they also recognized collagens with moderate avidity (Kd < 400 nM). After activation, the ¦ÁLI domain favored collagen I (Kd ¡Ö 80 nM) when compared to collagen IV. The integrin ¦ÁXI domain acted in a very different manner since already in native, wild-type form it bound to collagen IV and iC3b (Kd ¡Ö 200-400 nM). Antibodies against ¦ÁX¦Â2 and ¦ÁM¦Â2 blocked promyelocytic leukemia cell adhesion to the collagenous GFOGER motif, a binding site for the ¦Â1 integrin containing collagen receptors. In brief, leukocyte ¦Â2 integrins may act as collagen receptors in a heterodimer specific manner.