Post-translational processing of the leukocyte integrin alpha 4 beta 1.
The leukocyte integrin alpha 4 beta 1 (VLA-4, CD49d/CD29) is a receptor for the extracellular matrix protein fibronectin and the endothelial adhesion protein VCAM-1. We have analyzed the biosynthesis and post-translational modifications of the two subunits of this receptor complex. The alpha 4 subunit was initially synthesized as a single-chain polypeptide that underwent the formation of complex endoglycosidase H-resistant oligosaccharide side chains and which could be proteolytically cleaved into two noncovalently associated fragments. The level and rate of alpha 4 subunit cleavage was dependent on the cell studied. The T cell tumor line HPB-ALL expressed both intact and fragmented alpha 4 on the cell surface. The interleukin-2-dependent natural killer line NK 3.3 and long term interleukin-2-dependent activated T lymphocytes cleaved the alpha 4 polypeptide earlier and more efficiently than did HPB-ALL cells and did not have detectable levels of intact alpha 4 on the cell surface. The proteolysis of alpha 4 was blocked by treating cells with either the lysosomotrophic amine NH4Cl or the carboxylic ionophore monensin. The presence of complex N-linked oligosaccharides did not seem to be necessary for alpha 4 cleavage or for binding of the alpha 4 beta 1 complex to a synthetic peptide corresponding to the binding site for this receptor on fibronectin.
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D000939:Epitopes / Q000032:analysis; D005353:Fibronectins / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors; D006801:Humans; D015151:Immunoblotting; D039041:Integrin alpha4beta1; D016023:Integrins / Q000096:biosynthesis* / Q000235:genetics; D007376:Interleukin-2 / Q000494:pharmacology; D007962:Leukocytes / Q000502:physiology*; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D011480:Protease Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D016029:Receptors, Very Late Antigen / Q000096:biosynthesis* / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000939:Epitopes; D005353:Fibronectins; D039041:Integrin alpha4beta1; D016023:Integrins; D007376:Interleukin-2; D046911:Macromolecular Substances; D010455:Peptides; D011480:Protease Inhibitors; D016029:Receptors, Very Late Antigen; D006026:Glycoside Hydrolases