TY - JOUR
T1 - Binding of the integrin Mac-1 (CD11b/CD18) to the third immunoglobulin-like domain of ICAM-1 (CD54) and its regulation by glycosylation
AU - Diamond, Michael S.
AU - Staunton, Donald E.
AU - Marlin, Steven D.
AU - Springer, Timothy A.
N1 - Funding Information:
This work was supported by NIH grants (T32GM07753-11 and CA31799) and by Boehringer-lngelheim. The authors would like to thank Drs. P. Y. Chan and S. A. Stacker for their unbiased scoring, Dr. M. L. Hibbsfor her CD16-CD54chimericconstruct, A. R. de Fougerol-18s for the L-ICAM-I+ cells, and Ed Luther, Don Misumi, and Arun Gaur for their excellent technical assistance.
PY - 1991/6/14
Y1 - 1991/6/14
N2 - Both the integrins LFA-1 and Mac-1 bind to ICAM-1, an immunoglobulin superfamily member. Previously, we localized the binding sites of LFA-1 and the major group of human rhinoviruses to the first NH2-terminal immunoglobulin-like domain of ICAM-1. Here, we show that the binding site on ICAM-1 for Mac-1 is unexpectedly distinct from that for LFA-1 and maps to the third NH2-terminal immunoglobulin-like domain. These findings provide a function for the tandem duplication of immunoglobulin-like domains in ICAM-1 and have implications for other immunoglobulin superfamily members. Mutations at two sites in the third domain that destroy consensus sequences for N-linked glycosylation enhance binding to purified Mac-1. Agents that interfere with carbohydrate processing provide evidence that the size of the N-linked oligosaccharide side chains on ICAM-1 affects binding to Mac-1 but not to LFA-1. Thus, we suggest that the extent of glycosylation on ICAM-1 may regulate adhesion to LFA-1 or Mac-1 in vivo.
AB - Both the integrins LFA-1 and Mac-1 bind to ICAM-1, an immunoglobulin superfamily member. Previously, we localized the binding sites of LFA-1 and the major group of human rhinoviruses to the first NH2-terminal immunoglobulin-like domain of ICAM-1. Here, we show that the binding site on ICAM-1 for Mac-1 is unexpectedly distinct from that for LFA-1 and maps to the third NH2-terminal immunoglobulin-like domain. These findings provide a function for the tandem duplication of immunoglobulin-like domains in ICAM-1 and have implications for other immunoglobulin superfamily members. Mutations at two sites in the third domain that destroy consensus sequences for N-linked glycosylation enhance binding to purified Mac-1. Agents that interfere with carbohydrate processing provide evidence that the size of the N-linked oligosaccharide side chains on ICAM-1 affects binding to Mac-1 but not to LFA-1. Thus, we suggest that the extent of glycosylation on ICAM-1 may regulate adhesion to LFA-1 or Mac-1 in vivo.
UR - http://www.scopus.com/inward/record.url?scp=0025759969&partnerID=8YFLogxK
U2 - 10.1016/0092-8674(91)90548-D
DO - 10.1016/0092-8674(91)90548-D
M3 - Article
C2 - 1675157
AN - SCOPUS:0025759969
SN - 0092-8674
VL - 65
SP - 961
EP - 971
JO - Cell
JF - Cell
IS - 6
ER -