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PMID: 7542659 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Integrin beta 3 cytoplasmic tail is necessary and sufficient for regulation of alpha 5 beta 1 phagocytosis by alpha v beta 3 and integrin-associated protein.

The Journal of cell biology ·Vol. 130 ·No. 3 ·1995-08-00 ·Pages 745-54

Blystone SD, Lindberg FP, LaFlamme SE, Brown EJ

Abstract

Using a K562 cell transfection model, we have previously described a novel relationship between the integrins alpha v beta 3 and alpha 5 beta 1. alpha v beta 3 ligation was able to inhibit alpha 5 beta 1-mediated phagocytosis without effect on alpha 5 beta 1-mediated adhesion. The alpha v beta 3-dependent inhibition apparently required a signal transduction cascade as it was reversed by inhibitors of serine/threonine kinases. Now, we have studied the mechanisms of signal transduction in this system and have found that the beta 3 cytoplasmic tail is both necessary and sufficient for initiation of the signal leading to inhibition of alpha 5 beta 1 phagocytosis. Ligation of integrin-associated protein (IAP), which has been implicated in alpha v beta 3 signal transduction, mimics the effects of alpha v beta 3 ligation only when the beta 3 integrin with an intact cytoplasmic tail is present. Although fibronectin-mediated phagocytosis requires the high affinity conformation of alpha 5 beta 1, ligation of alpha v beta 3/IAP does not prevent acquisition of this high affinity state. We conclude that alpha v beta 3/IAP ligation initates a signal transduction cascade, dependent upon the beta 3 cytoplasmic tail, which inhibits the phagocytic function of alpha 5 beta 1 at a step subsequent to modulation of integrin affinity.

MeSH Terms
Antigens, CD/metabolism CD47 Antigen Carrier Proteins/metabolism Cell Adhesion/physiology Epitopes Humans Integrin beta3 Integrins/immunology,metabolism Leukemia, Erythroblastic, Acute Ligands Peptide Fragments/metabolism Phagocytosis/physiology Platelet Glycoprotein GPIIb-IIIa Complex Receptors, Cytoadhesin/metabolism Receptors, Fibronectin/metabolism Receptors, Vitronectin Recombinant Proteins/metabolism Signal Transduction/physiology Structure-Activity Relationship Transfection Tumor Cells, Cultured
Chemicals
Antigens, CD CD47 Antigen CD47 protein, human Carrier Proteins Epitopes Integrin beta3 Integrins Ligands Peptide Fragments Platelet Glycoprotein GPIIb-IIIa Complex Receptors, Cytoadhesin Receptors, Fibronectin Receptors, Vitronectin Recombinant Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Blystone S D
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Lindberg F P
LaFlamme S E
Brown E J
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.130.3.745
Published
1995-08-00
Pages
745-54
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2120530
Subset
IM
Grants
NIAID NIH HHS · AI08990-02 · United States
NIAID NIH HHS · AI24674 · United States
NIGMS NIH HHS · GM38330 · United States
External Links
PubMed source DOI: 10.1083/jcb.130.3.745 PMC Full Text View journal details
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