Effect of cytoplasmic domain mutations on the agonist-stimulated ligand binding activity of the platelet integrin alphaIIbbeta3.

The Journal of Biological Chemistry
E LohJ S Bennett

Abstract

Function of the platelet integrin alphaIIbbeta3 is regulated by agonist-generated signals interacting with its cytoplasmic tails. When alphaIIbbeta3 is expressed in Epstein-Barr virus-transformed B lymphocytes, stimulation of the cells with phorbol 12-myristate 13-acetate results in alphaIIbbeta3-mediated lymphocyte adherence to immobilized fibrinogen, as well as soluble fibrinogen binding to alphaIIbbeta3, indicating that agonists increase the affinity of alphaIIbbeta3 for fibrinogen in these cells. To address the contribution of the alphaIIb and beta3 cytoplasmic tails to this process, we mutated each tail and expressed the mutants in B lymphocytes. Truncation of the alphaIIb tail did not impair unstimulated or stimulated lymphocyte adherence to fibrinogen, regardless whether the truncation was proximal or distal to the conserved GFFKR sequence. However, deleting GFFKR or replacing it with alanines markedly reduced alphaIIbbeta3 expression due to impaired intracellular assembly of alphaIIbbeta3 heterodimers, probably due to a mutation-induced change in the conformation of alphaIIb. Introducing beta3 mutations known to impair alphaIIbbeta3 function in platelets into the cytoplasmic tail of beta3 in lymphocytes also impaired al...Continue Reading

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Citations

Oct 23, 1997·Current Opinion in Cell Biology·W Kolanus, B Seed
Oct 19, 2001·Proceedings of the National Academy of Sciences of the United States of America·R LiW F DeGrado
May 20, 1998·American Heart Journal·M Quinn, D J Fitzgerald
Mar 28, 1997·The Journal of Biological Chemistry·J S BennettW F DeGrado
Aug 4, 2011·Journal of Thrombosis and Haemostasis : JTH·A Nurden, P Nurden
Feb 7, 2002·The Journal of Biological Chemistry·Simone M SchoenwaelderShaun P Jackson
Jun 17, 1998·The Journal of Biological Chemistry·W QiJ S Bennett

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