Dualistic nature of adhesive protein function: fibronectin and its biologically active peptide fragments can autoinhibit fibronectin function

doi:10.1083/jcb.99.1.29

This Article

	Full Text (PDF, 999K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JCB
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Yamada, K.
	Articles by Kennedy, D.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Yamada, K.
	Articles by Kennedy, D.


Social Bookmarking

	What's this?

ARTICLES

Dualistic nature of adhesive protein function: fibronectin and its biologically active peptide fragments can autoinhibit fibronectin function

KM Yamada and DW Kennedy

Fibronectin and certain polypeptide regions of this adhesive glycoprotein mediate cell attachment and spreading on various substrates. We explored the theoretical prediction that this adhesive protein could become a competitive inhibitor of fibronectin-mediated processes if present in solution at appropriately high concentrations. Fibronectin function was inhibited by purified plasma fibronectin at 5- 10 mg/ml, by a 75,000-dalton cell-interaction fragment of the protein at 0.5-1 mg/ml, and even by two synthetic peptides containing a conserved, hydrophilic amino acid sequence at 0.1-0.5 mg/ml. Inhibition of fibronectin-dependent cell spreading was dose dependent, noncytotoxic, and reversible. It was competitive in nature, since increased quantities of substrate-adsorbed fibronectin or longer incubation periods decreased the inhibition. A peptide inhibitory for fibronectin-mediated cell spreading also inhibited fibronectin-mediated attachment of cells to type I collagen, but it did not affect concanavalin A-mediated spreading. These results demonstrate the potential of a cell adhesion molecule and its biologically active peptide fragments to act as competitive inhibitors, and they suggest that fibronectin may act by binding to a saturable cell surface receptor.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Loscertales, M., Mikels, A. J., Hu, J. K.-H., Donahoe, P. K., Roberts, D. J. (2008). Chick pulmonary Wnt5a directs airway and vascular tubulogenesis. Development 135: 1365-1376 [Abstract] [Full Text]
Koblinski, J. E., Wu, M., Demeler, B., Jacob, K., Kleinman, H. K. (2005). Matrix cell adhesion activation by non-adhesion proteins. J. Cell Sci. 118: 2965-2974 [Abstract] [Full Text]
Bae, E., Sakai, T., Mosher, D. F. (2004). Assembly of Exogenous Fibronectin by Fibronectin-null Cells Is Dependent on the Adhesive Substrate. J. Biol. Chem. 279: 35749-35759 [Abstract] [Full Text]
McGrath, M. J., Mitchell, C. A., Coghill, I. D., Robinson, P. A., Brown, S. (2003). Skeletal muscle LIM protein 1 (SLIM1/FHL1) induces {alpha}5{beta}1-integrin-dependent myocyte elongation. Am. J. Physiol. Cell Physiol. 285: C1513-C1526 [Abstract] [Full Text]
Levy, Y., Ronen, D., Bershadsky, A. D., Zick, Y. (2003). Sustained Induction of ERK, Protein Kinase B, and p70 S6 Kinase Regulates Cell Spreading and Formation of F-actin Microspikes Upon Ligation of Integrins by Galectin-8, a Mammalian Lectin. J. Biol. Chem. 278: 14533-14542 [Abstract] [Full Text]
Robinson, P. A., Brown, S., McGrath, M. J., Coghill, I. D., Gurung, R., Mitchell, C. A. (2003). Skeletal muscle LIM protein 1 regulates integrin-mediated myoblast adhesion, spreading, and migration. Am. J. Physiol. Cell Physiol. 284: C681-C695 [Abstract] [Full Text]
Thomas, G., Speight, P.M. (2001). Cell Adhesion Molecules and Oral Cancer. CROBM 12: 479-498 [Abstract] [Full Text]
Paine, E., Palmantier, R., Akiyama, S. K., Olden, K., Roberts, J. D. (2000). Arachidonic Acid Activates Mitogen-activated Protein (MAP) Kinase-activated Protein Kinase 2 and Mediates Adhesion of a Human Breast Carcinoma Cell Line to Collagen Type IV through a p38 MAP Kinase-dependent Pathway. J. Biol. Chem. 275: 11284-11290 [Abstract] [Full Text]
Disatnik, M.-H., Rando, T. A. (1999). Integrin-mediated Muscle Cell Spreading. THE ROLE OF PROTEIN KINASE C IN OUTSIDE-IN AND INSIDE-OUT SIGNALING AND EVIDENCE OF INTEGRIN CROSS-TALK. J. Biol. Chem. 274: 32486-32492 [Abstract] [Full Text]
Liao, Y.-F., Wieder, K. G., Classen, J. M., De Water, L. V. (1999). Identification of Two Amino Acids within the EIIIA (ED-A) Segment of Fibronectin Constituting the Epitope for Two Function-blocking Monoclonal Antibodies. J. Biol. Chem. 274: 17876-17884 [Abstract] [Full Text]
Mould, A. P., Burrows, L., Humphries, M. J. (1998). Identification of Amino Acid Residues That Form Part of the Ligand-binding Pocket of Integrin alpha 5beta 1. J. Biol. Chem. 273: 25664-25672 [Abstract] [Full Text]
Eberhard, T., Virkola, R., Korhonen, T., Kronvall, G., Ullberg, M. (1998). Binding to Human Extracellular Matrix by Neisseria meningitidis. Infect. Immun. 66: 1791-1794 [Abstract] [Full Text]
Stanton, H, Gavrilovic, J, Atkinson, S., d'Ortho, M., Yamada, K., Zardi, L, Murphy, G (1998). The activation of ProMMP-2 (gelatinase A) by HT1080 fibrosarcoma cells is promoted by culture on a fibronectin substrate and is concomitant with an increase in processing of MT1-MMP (MMP-14) to a 45 kDa form. J. Cell Sci. 111: 2789-2798 [Abstract]
Ganta, D. R., McCarthy, M.-B., Gronowicz, G. A. (1997). Ascorbic Acid Alters Collagen Integrins in Bone Culture. Endocrinology 138: 3606-3612 [Abstract] [Full Text]
Tselepis, V. H., Green, L. J., Humphries, M. J. (1997). An RGD to LDV Motif Conversion within the Disintegrin Kistrin Generates an Integrin Antagonist That Retains Potency but Exhibits Altered Receptor Specificity. EVIDENCE FOR A FUNCTIONAL EQUIVALENCE OF ACIDIC INTEGRIN-BINDING MOTIFS. J. Biol. Chem. 272: 21341-21348 [Abstract] [Full Text]
Mould, A. P., Askari, J. A., Aota, S.-i., Yamada, K. M., Irie, A., Takada, Y., Mardon, H. J., Humphries, M. J. (1997). Defining the Topology of Integrin alpha 5beta 1-Fibronectin Interactions Using Inhibitory Anti-alpha 5 and Anti-beta 1 Monoclonal Antibodies. EVIDENCE THAT THE SYNERGY SEQUENCE OF FIBRONECTIN IS RECOGNIZED BY THE AMINO-TERMINAL REPEATS OF THE alpha 5 SUBUNIT. J. Biol. Chem. 272: 17283-17292 [Abstract] [Full Text]
Cui, L., Yu, W.-P., DeAizpurua, H. J., Schmidli, R. S., Pallen, C. J. (1996). Cloning and Characterization of Islet Cell Antigen-related Protein-tyrosine Phosphatase (PTP), a Novel Receptor-like PTP and Autoantigen in Insulin-dependent Diabetes. J. Biol. Chem. 271: 24817-24823 [Abstract] [Full Text]
Mould, A. P., Akiyama, S. K., Humphries, M. J. (1996). The Inhibitory Anti-beta 1 Integrin Monoclonal Antibody 13Recognizes an Epitope That Is Attenuated by Ligand Occupancy. EVIDENCE FOR ALLOSTERIC INHIBITION OF INTEGRIN FUNCTION. J. Biol. Chem. 271: 20365-20374 [Abstract] [Full Text]
Mould, A. P., Akiyama, S. K., Humphries, M. J. (1995). Regulation of Integrin alpha5beta1-Fibronectin Interactions by Divalent Cations. J. Biol. Chem. 270: 26270-26277 [Abstract] [Full Text]
Danen, E. H. J., Aota, S.-i., van Kraats, A. A., Yamada, K. M., Ruiter, D. J., van Muijen, G. N. P. (1995). Requirement for the Synergy Site for Cell Adhesion to Fibronectin Depends on the Activation State of Integrin alpha5beta1. J. Biol. Chem. 270: 21612-21618 [Abstract] [Full Text]
Hanein, D, Sabanay, H, Addadi, L, Geiger, B (1993). Selective interactions of cells with crystal surfaces. Implications for the mechanism of cell adhesion. J. Cell Sci. 104: 275-288 [Abstract]
Bunch, T., Brower, D. (1992). Drosophila PS2 integrin mediates RGD-dependent cell-matrix interactions. Development 116: 239-247 [Abstract]
Yamada, K.M., Aota, S., Akiyama, S.K., LaFlamme, S.E. (1992). Mechanisms of Fibronectin and Integrin Function during Cell Adhesion and Migration. Cold Spring Harb Symp Quant Biol 57: 203-212 [Abstract]
Slavkin, H. C. (1990). Molecular Determinants of Tooth Development: A Review. CROBM 1: 1-16 [Full Text]
Slavkin, H.C. (1988). Gene Regulation in the Development of Oral Tissues. JDR 67: 1142-1149 [Abstract]
Ruoslahti, E, Pierschbacher, M. (1987). New perspectives in cell adhesion: RGD and integrins. Science 238: 491-497 [Abstract]
Humphries, M., Olden, K, Yamada, K. (1986). A synthetic peptide from fibronectin inhibits experimental metastasis of murine melanoma cells. Science 233: 467-470 [Abstract]
Pytela, R, Pierschbacher, M., Ginsberg, M., Plow, E., Ruoslahti, E (1986). Platelet membrane glycoprotein IIb/IIIa: member of a family of Arg-Gly-Asp--specific adhesion receptors. Science 231: 1559-1562 [Abstract]
Mould, A. P., Askari, J. A., Humphries, M. J. (2000). Molecular Basis of Ligand Recognition by Integrin alpha 5beta 1. I. SPECIFICITY OF LIGAND BINDING IS DETERMINED BY AMINO ACID SEQUENCES IN THE SECOND AND THIRD NH2-TERMINAL REPEATS OF THE alpha SUBUNIT. J. Biol. Chem. 275: 20324-20336 [Abstract] [Full Text]
Levy, Y., Arbel-Goren, R., Hadari, Y. R., Eshhar, S., Ronen, D., Elhanany, E., Geiger, B., Zick, Y. (2001). Galectin-8 Functions as a Matricellular Modulator of Cell Adhesion. J. Biol. Chem. 276: 31285-31295 [Abstract] [Full Text]
Coe, A. P. F., Askari, J. A., Kline, A. D., Robinson, M. K., Kirby, H., Stephens, P. E., Humphries, M. J. (2001). Generation of a Minimal alpha 5beta 1 Integrin-Fc Fragment. J. Biol. Chem. 276: 35854-35866 [Abstract] [Full Text]