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Identification of critical amino-acid residues on the erythroid intercellular adhesion molecule-4 (ICAM-4) mediating adhesion to alpha V integrins.
Blood. 2004 Feb 15; 103(4):1503-8.Blood

Abstract

Intercellular adhesion molecule-4 (ICAM-4, syn. LW glycoprotein) interacts with the integrins alpha(L)beta(2), alpha(M)beta(2), A(4)beta(1), the alpha(V) family, and alpha(IIb)beta(3). Systematic mutagenesis of surface-exposed residues conserved between human and murine ICAM-4 defined 12 single amino-acid changes that affect the interaction of ICAM-4 with alpha(V) integrins. Mutation of 10 of these residues, 8 of which are spatially close on the surface of the molecule, led to a reduction in adhesion. Moreover, peptides corresponding to regions of ICAM-4 involved in its interaction with alpha(V) integrins inhibited these interactions. The other 2 mutations increased the extent of interaction of ICAM-4 with alpha(V) integrins. These mutations appear to prevent glycosylation of N160, suggesting that changes in glycosylation may modulate ICAM-4-alpha(V) integrin interactions. The region of ICAM-4 identified as the binding site for alpha(V) integrins is adjacent to the binding sites for alpha(L)beta(2) and alpha(M)beta(2). Selective binding of ICAM-4 to different integrins may be important for a variety of normal red cell functions and also relevant to the pathology of thrombotic disorders and vasoocclusive events in sickle cell disease. Our findings suggest the feasibility of developing selective inhibitors of ICAM-4-integrin adhesion of therapeutic value in these diseases.

Authors+Show Affiliations

Bristol Institute for Transfusion Sciences, Southmead Rd, Bristol, BS10 5ND, UK. tosti.mankelow@nbs.nhs.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14551135

Citation

Mankelow, Tosti J., et al. "Identification of Critical Amino-acid Residues On the Erythroid Intercellular Adhesion Molecule-4 (ICAM-4) Mediating Adhesion to Alpha V Integrins." Blood, vol. 103, no. 4, 2004, pp. 1503-8.
Mankelow TJ, Spring FA, Parsons SF, et al. Identification of critical amino-acid residues on the erythroid intercellular adhesion molecule-4 (ICAM-4) mediating adhesion to alpha V integrins. Blood. 2004;103(4):1503-8.
Mankelow, T. J., Spring, F. A., Parsons, S. F., Brady, R. L., Mohandas, N., Chasis, J. A., & Anstee, D. J. (2004). Identification of critical amino-acid residues on the erythroid intercellular adhesion molecule-4 (ICAM-4) mediating adhesion to alpha V integrins. Blood, 103(4), 1503-8.
Mankelow TJ, et al. Identification of Critical Amino-acid Residues On the Erythroid Intercellular Adhesion Molecule-4 (ICAM-4) Mediating Adhesion to Alpha V Integrins. Blood. 2004 Feb 15;103(4):1503-8. PubMed PMID: 14551135.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of critical amino-acid residues on the erythroid intercellular adhesion molecule-4 (ICAM-4) mediating adhesion to alpha V integrins. AU - Mankelow,Tosti J, AU - Spring,Frances A, AU - Parsons,Stephen F, AU - Brady,R Leo, AU - Mohandas,Narla, AU - Chasis,Joel A, AU - Anstee,David J, Y1 - 2003/10/09/ PY - 2003/10/11/pubmed PY - 2004/3/19/medline PY - 2003/10/11/entrez SP - 1503 EP - 8 JF - Blood JO - Blood VL - 103 IS - 4 N2 - Intercellular adhesion molecule-4 (ICAM-4, syn. LW glycoprotein) interacts with the integrins alpha(L)beta(2), alpha(M)beta(2), A(4)beta(1), the alpha(V) family, and alpha(IIb)beta(3). Systematic mutagenesis of surface-exposed residues conserved between human and murine ICAM-4 defined 12 single amino-acid changes that affect the interaction of ICAM-4 with alpha(V) integrins. Mutation of 10 of these residues, 8 of which are spatially close on the surface of the molecule, led to a reduction in adhesion. Moreover, peptides corresponding to regions of ICAM-4 involved in its interaction with alpha(V) integrins inhibited these interactions. The other 2 mutations increased the extent of interaction of ICAM-4 with alpha(V) integrins. These mutations appear to prevent glycosylation of N160, suggesting that changes in glycosylation may modulate ICAM-4-alpha(V) integrin interactions. The region of ICAM-4 identified as the binding site for alpha(V) integrins is adjacent to the binding sites for alpha(L)beta(2) and alpha(M)beta(2). Selective binding of ICAM-4 to different integrins may be important for a variety of normal red cell functions and also relevant to the pathology of thrombotic disorders and vasoocclusive events in sickle cell disease. Our findings suggest the feasibility of developing selective inhibitors of ICAM-4-integrin adhesion of therapeutic value in these diseases. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/14551135/Identification_of_critical_amino_acid_residues_on_the_erythroid_intercellular_adhesion_molecule_4__ICAM_4__mediating_adhesion_to_alpha_V_integrins_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-4971(20)50181-X DB - PRIME DP - Unbound Medicine ER -