title: Activation-dependent recognition by hematopoietic cells of the LDV sequence in the V region of fibronectin.
abstract: It has been shown that the alpha 4 beta 1 integrin is the lymphocyte receptor for the carboxy terminal cell-binding domain of fibronectin which comprises adhesion sites in Hep 2 and a high affinity site, CS-1, in the type III connecting segment or V (for variable) region. In the present studies, using a series of peptides derived from CS-1, we identify the tripeptide leu-asp-val (LDV), as the minimal peptide capable of supporting stable lymphocyte or melanoma cell adhesion. However, only cells which expressed an active form of the alpha 4 beta 1 complex were capable of attaching to and spreading on LDV peptide. On a molar basis, LDV minimal peptides were either not active or 10-20 times less active than intact CS-1 in promoting the adhesion of lymphocytes expressing the resting form of the receptor. In cells which express the high avidity form of the receptor, LDV and CS-1 were equally effective in promoting cell adhesion and spreading. The avidity of the alpha 4 beta 1 complex could be altered with mAbs to beta 1 which specifically activate beta 1 dependent function. The high avidity form of the alpha 4 beta 1 complex could be induced on U937 cells, T, and B lymphoblastoid cell lines, or PHA-stimulated T cell blasts. Resting PBL could not be induced to bind LDV peptide conjugates by activating antibodies to beta 1 implying that two signals are required for LDV recognition by T cells. In conclusion, these data show clearly that the minimal peptide for the alpha 4 beta 1 complex in CS-1 is the LDV sequence. Although numerous cell populations can interact with intact CS-1 only cells which express an active alpha 4 beta 1 complex can bind the LDV sequence. This implies that cell interaction with the carboxy terminal cell-binding domain of fibronectin can be regulated at several levels: (a) alpha 4 beta 1 expression; (b) activation of the alpha 4 beta 1 complex; and (c) alternate splicing of CS-1 into V+ isoforms of fibronectin.
authors.affiliation: University of Minnesota, Department of Laboratory Medicine and Pathology, Minneapolis 55455.
authors.forename: E A
authors.initials: EA
authors.lastname: Wayner
authors.forename: N L
authors.initials: NL
authors.lastname: Kovach
mesh_terms: D000595:Amino Acid Sequence; D002448:Cell Adhesion; D005353:Fibronectins / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000502:physiology*; D008024:Ligands; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000166:cytology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D005353:Fibronectins; D016023:Integrins; D008024:Ligands; D010455:Peptides; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic