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Gene Review

Fn1  -  fibronectin 1

Mus musculus

Synonyms: E330027I09, FN, Fibronectin, Fn, Fn-1
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Disease relevance of Fn1


High impact information on Fn1


Chemical compound and disease context of Fn1


Biological context of Fn1

  • A detailed analysis of the molecular mechanisms involved in N1 and N7 cell adhesion to ECM substrata was performed by using antibodies raised against the FN receptor and synthetic peptides variously competing with the FN or VN binding to integrin receptor (GRGDSP and GRGESP) [14].
  • Furthermore, our data suggest that FN acts synergistically with IgE to prolong intracellular phosphorylation events and to enhance IgE-induced inflammatory cytokine production and BMMC survival [15].
  • Whereas cytokines activated resting progenitor cells to migrate on ECM, cell migration speed was regulated by Fn concentration [16].
  • Fibronectin splice variants containing the EIIIA and/or EIIIB exons are prominently expressed in the vasculature of a variety of human tumors but not in normal adult tissues [17].
  • Costimulation of fibronectin receptor promotes Fc gamma R-mediated rescue of IL-3-dependent bone marrow-derived cells from apoptosis [18].

Anatomical context of Fn1

  • Exogenous provision of RA or Fn to Raldh2(-/-) explants in whole mouse embryo culture restored vascular remodeling, visceral endoderm survival, as well as integrin alpha5 expression and its downstream signaling that controls endothelial growth [19].
  • Parental cells and cells expressing wild-type PTP1B show similar morphology, are able to attach and spread on fibronectin, and form focal adhesions and stress fibers [20].
  • FN-induced cytoskeletal rearrangement was retarded in PTP alpha-/- cells, with delayed filamentous actin stress fiber assembly and focal adhesion formation [21].
  • However, these anti-adhesive treatments, while ineffective on Vrest of N7 cells, abolished in N1 cells the FN- or VN-induced hyperpolarization and neurite outgrowth, that appeared therefore strictly associated and integrin-mediated phenomena [14].
  • These data suggest that FN-binding integrins on T cells play a role in the localization of T cells to sites of antigenic challenge in tissue [22].

Associations of Fn1 with chemical compounds

  • Antibodies, as well as GRGDSP, abolished adhesion of N1 and N7 clones to FN and VN, revealing a similar implication of integrins in the adhesion of these clones to the ECM proteins [14].
  • We demonstrate that the cells that transfer CHS to TNCB adhere to FN in the presence of Ca2+/Mg2+, and T-cell populations depleted of FN-adherent cells do not transfer immunity [22].
  • Furthermore, these effects of FN are blocked specifically by RGD peptide or anti-VLA-4 mAb [18].
  • FAK catalytic activity, proline-rich domains, and location in focal contacts were all required for proper allocation and patterning of FN matrix [23].
  • High glucose also increased fibronectin message and protein [9].
  • Analysis of beta1-integrin-receptor-null fibroblasts, blockage of cell surface integrin receptors that regulate fibronectin assembly and disruption of Rho kinase all result in suppressed deposition of both fibronectin and microfibrils [24].

Physical interactions of Fn1


Enzymatic interactions of Fn1

  • Nuclear detection of Smad3 and phosphorylated Smads within intraluminal fibroblasts coincided with increased intraluminal deposition of fibronectin and collagen [28].
  • It was found that FCS and fibronectin stimulated phosphorylating activity of FAK in the cells at the logarithmic phase of growth, but were inefficient in the confluent cells [29].
  • The protein appears to be located in focal contacts where it codistributes with beta 1 integrins. pp120 is distinct from the beta 1 subunit of integrins and from vinculin and alpha-actinin. pp120 is rapidly dephosphorylated in cells suspended by trypsinization but becomes rapidly phosphorylated in cells attaching and spreading on fibronectin [30].
  • Effects of fibronectin cleaved by neuropsin on cell adhesion and migration [31].

Co-localisations of Fn1


Regulatory relationships of Fn1

  • FAK promotes organization of fibronectin matrix and fibrillar adhesions [23].
  • These data demonstrate that trafficking of alphaIIb regulates adhesion between trophoblast cells and fibronectin as invasion of the endometrium commences [35].
  • Reduction in fibronectin expression and alteration in cell morphology are coincident in NIH3T3 cells expressing a mutant E2F1 transcription factor [36].
  • RESULTS: TGF-beta up-regulated FN mRNA accumulation in a time- and dose-dependent manner, which was completely inhibited by phosphatidylcholine-phospholipase C (PC-PLC) inhibitor and PKC inhibitors (calphostin-C and staurosporin) [37].
  • Transition from condensation to overt cell differentiation is under both positive and negative control (Fig. 3). Syndecan blocks fibronectin and so blocks N-CAM accumulation, preventing accumulation of additional cell[38]

Other interactions of Fn1

  • Interestingly, we found, using the calcium channel blocker, 2-APB (2-aminoethoxydiphenyl borate) and Lyn-/- BMMCs that both IgE- and IgE + Ag-induced adhesion to FN require extracellular calcium entry, whereas SF does not [15].
  • Mast cells from c-kit mutant mice adhere to fibronectin on stimulation with phorbol 12-myristate 13-acetate (PMA), but not on stimulation with steel factor, indicating that stimulation of integrin adhesiveness requires activation of the c-kit protein tyrosine kinase [39].
  • To directly test the function of EIIIA-FN, we generated EIIIA-null (EIIIA(-/-)) mice that lack the EIIIA exon and crossed them with apolipoprotein E (ApoE)-null (ApoE(-/-)) mice that develop arterial wall lesions [40].
  • Furthermore, we showed that maspin directly increased endodermal cell adhesion to laminin matrix but not to fibronectin [41].
  • Laminin, entactin/nidogen, and fibronectin immunoreactivities were similarly ubiquitous on tumor vessels [42].

Analytical, diagnostic and therapeutic context of Fn1


  1. Pancreas recovery following cerulein-induced pancreatitis is impaired in plasminogen-deficient mice. Lugea, A., Nan, L., French, S.W., Bezerra, J.A., Gukovskaya, A.S., Pandol, S.J. Gastroenterology (2006) [Pubmed]
  2. Deletion of Protein Kinase C-{beta} Isoform In Vivo Reduces Renal Hypertrophy but Not Albuminuria in the Streptozotocin-Induced Diabetic Mouse Model. Meier, M., Park, J.K., Overheu, D., Kirsch, T., Lindschau, C., Gueler, F., Leitges, M., Menne, J., Haller, H. Diabetes (2007) [Pubmed]
  3. Antigen-independent processes in antigen-specific immunity. A role for alpha 4 integrin. Ferguson, T.A., Kupper, T.S. J. Immunol. (1993) [Pubmed]
  4. Inhibition of metastatic cell colonization in murine lungs and tumor-induced morbidity by non-peptidic Arg-Gly-Asp mimetics. Hardan, I., Weiss, L., Hershkoviz, R., Greenspoon, N., Alon, R., Cahalon, L., Reich, S., Slavin, S., Lider, O. Int. J. Cancer (1993) [Pubmed]
  5. Fibronectin-binding protein I of Streptococcus pyogenes is a promising adjuvant for antigens delivered by mucosal route. Medina, E., Talay, S.R., Chhatwal, G.S., Guzmán, C.A. Eur. J. Immunol. (1998) [Pubmed]
  6. Periodic lamellipodial contractions correlate with rearward actin waves. Giannone, G., Dubin-Thaler, B.J., Döbereiner, H.G., Kieffer, N., Bresnick, A.R., Sheetz, M.P. Cell (2004) [Pubmed]
  7. Stereocilia defects in the sensory hair cells of the inner ear in mice deficient in integrin alpha8beta1. Littlewood Evans, A., Müller, U. Nat. Genet. (2000) [Pubmed]
  8. Lymphoid cells recognize an alternatively spliced segment of fibronectin via the integrin receptor alpha 4 beta 1. Guan, J.L., Hynes, R.O. Cell (1990) [Pubmed]
  9. Cultured tubule cells from TGF-beta1 null mice exhibit impaired hypertrophy and fibronectin expression in high glucose. Chen, S., Hoffman, B.B., Lee, J.S., Kasama, Y., Jim, B., Kopp, J.B., Ziyadeh, F.N. Kidney Int. (2004) [Pubmed]
  10. Fibronectin receptor defects in NOD mouse leucocytes: possible consequences for type 1 diabetes. Geutskens, S.B., Mendes-da-Cruz, D.A., Dardenne, M., Savino, W. Scand. J. Immunol. (2004) [Pubmed]
  11. Cell surface phosphatidylinositol-anchored heparan sulfate proteoglycan initiates mouse melanoma cell adhesion to a fibronectin-derived, heparin-binding synthetic peptide. Drake, S.L., Klein, D.J., Mickelson, D.J., Oegema, T.R., Furcht, L.T., McCarthy, J.B. J. Cell Biol. (1992) [Pubmed]
  12. Modulation of melanoma cell adhesion to basement membrane components by retinoic acid. Edward, M., Gold, J.A., MacKie, R.M. J. Cell. Sci. (1989) [Pubmed]
  13. Paricalcitol attenuates renal interstitial fibrosis in obstructive nephropathy. Tan, X., Li, Y., Liu, Y. J. Am. Soc. Nephrol. (2006) [Pubmed]
  14. Integrin-mediated neurite outgrowth in neuroblastoma cells depends on the activation of potassium channels. Arcangeli, A., Becchetti, A., Mannini, A., Mugnai, G., De Filippi, P., Tarone, G., Del Bene, M.R., Barletta, E., Wanke, E., Olivotto, M. J. Cell Biol. (1993) [Pubmed]
  15. IgE alone stimulates mast cell adhesion to fibronectin via pathways similar to those used by IgE + antigen but distinct from those used by Steel factor. Lam, V., Kalesnikoff, J., Lee, C.W., Hernandez-Hansen, V., Wilson, B.S., Oliver, J.M., Krystal, G. Blood (2003) [Pubmed]
  16. Adhesion and migration are differentially regulated in hematopoietic progenitor cells by cytokines and extracellular matrix. Strobel, E.S., Möbest, D., von Kleist, S., Dangel, M., Ries, S., Mertelsmann, R., Henschler, R. Blood (1997) [Pubmed]
  17. Direct test of potential roles of EIIIA and EIIIB alternatively spliced segments of fibronectin in physiological and tumor angiogenesis. Astrof, S., Crowley, D., George, E.L., Fukuda, T., Sekiguchi, K., Hanahan, D., Hynes, R.O. Mol. Cell. Biol. (2004) [Pubmed]
  18. Costimulation of fibronectin receptor promotes Fc gamma R-mediated rescue of IL-3-dependent bone marrow-derived cells from apoptosis. Yoshikawa, H., Sakihama, T., Nakajima, Y., Tasaka, K. J. Immunol. (1996) [Pubmed]
  19. Signaling hierarchy downstream of retinoic acid that independently regulates vascular remodeling and endothelial cell proliferation. Bohnsack, B.L., Lai, L., Dolle, P., Hirschi, K.K. Genes Dev. (2004) [Pubmed]
  20. Impaired integrin-mediated adhesion and signaling in fibroblasts expressing a dominant-negative mutant PTP1B. Arregui, C.O., Balsamo, J., Lilien, J. J. Cell Biol. (1998) [Pubmed]
  21. PTP alpha regulates integrin-stimulated FAK autophosphorylation and cytoskeletal rearrangement in cell spreading and migration. Zeng, L., Si, X., Yu, W.P., Le, H.T., Ng, K.P., Teng, R.M., Ryan, K., Wang, D.Z., Ponniah, S., Pallen, C.J. J. Cell Biol. (2003) [Pubmed]
  22. Two integrin-binding peptides abrogate T cell-mediated immune responses in vivo. Ferguson, T.A., Mizutani, H., Kupper, T.S. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  23. FAK promotes organization of fibronectin matrix and fibrillar adhesions. Ilić, D., Kovacic, B., Johkura, K., Schlaepfer, D.D., Tomasević, N., Han, Q., Kim, J.B., Howerton, K., Baumbusch, C., Ogiwara, N., Streblow, D.N., Nelson, J.A., Dazin, P., Shino, Y., Sasaki, K., Damsky, C.H. J. Cell. Sci. (2004) [Pubmed]
  24. Fibrillin-1 microfibril deposition is dependent on fibronectin assembly. Kinsey, R., Williamson, M.R., Chaudhry, S., Mellody, K.T., McGovern, A., Takahashi, S., Shuttleworth, C.A., Kielty, C.M. J. Cell. Sci. (2008) [Pubmed]
  25. Identification of a novel recognition sequence for fibronectin within the NH2-terminal beta-sandwich domain of tissue transglutaminase. Hang, J., Zemskov, E.A., Lorand, L., Belkin, A.M. J. Biol. Chem. (2005) [Pubmed]
  26. Analysis of integrin receptors for laminin and type IV collagen on metastatic B16 melanoma cells. Ramos, D.M., Berston, E.D., Kramer, R.H. Cancer Res. (1990) [Pubmed]
  27. Expression of fibronectin and a fibronectin-binding molecule during preimplantation development in the mouse. Morin, N., Sullivan, R. Hum. Reprod. (1994) [Pubmed]
  28. Smad3 deficiency ameliorates experimental obliterative bronchiolitis in a heterotopic tracheal transplantation model. Ramirez, A.M., Takagawa, S., Sekosan, M., Jaffe, H.A., Varga, J., Roman, J. Am. J. Pathol. (2004) [Pubmed]
  29. Signal transduction in confluent C3H 10T1/2 cells. The role of focal adhesion kinase. Miłoszewska, J., Trembacz, H., Janik, P. Acta Biochim. Pol. (2001) [Pubmed]
  30. Fibronectin/integrin interaction induces tyrosine phosphorylation of a 120-kDa protein. Guan, J.L., Trevithick, J.E., Hynes, R.O. Cell Regul. (1991) [Pubmed]
  31. Effects of fibronectin cleaved by neuropsin on cell adhesion and migration. Tani, N., Matsumoto, K., Ota, I., Yoshida, S., Takada, Y., Shiosaka, S., Matsuura, N. Neurosci. Res. (2001) [Pubmed]
  32. Expression of the integrin subunit alpha8 in murine lung development. Wagner, T.E., Frevert, C.W., Herzog, E.L., Schnapp, L.M. J. Histochem. Cytochem. (2003) [Pubmed]
  33. Cell surface localization of tissue transglutaminase is dependent on a fibronectin-binding site in its N-terminal beta-sandwich domain. Gaudry, C.A., Verderio, E., Aeschlimann, D., Cox, A., Smith, C., Griffin, M. J. Biol. Chem. (1999) [Pubmed]
  34. NG2 glial cells provide a favorable substrate for growing axons. Yang, Z., Suzuki, R., Daniels, S.B., Brunquell, C.B., Sala, C.J., Nishiyama, A. J. Neurosci. (2006) [Pubmed]
  35. Alpha5beta1, alphaVbeta3 and the platelet-associated integrin alphaIIbbeta3 coordinately regulate adhesion and migration of differentiating mouse trophoblast cells. Rout, U.K., Wang, J., Paria, B.C., Armant, D.R. Dev. Biol. (2004) [Pubmed]
  36. Reduction in fibronectin expression and alteration in cell morphology are coincident in NIH3T3 cells expressing a mutant E2F1 transcription factor. Jordan-Sciutto, K.L., Logan, T.J., Norton, P.A., Derfoul, A., Dodge, G.R., Hall, D.J. Exp. Cell Res. (1997) [Pubmed]
  37. Involvement of HB-EGF and EGF receptor transactivation in TGF-beta-mediated fibronectin expression in mesangial cells. Uchiyama-Tanaka, Y., Matsubara, H., Mori, Y., Kosaki, A., Kishimoto, N., Amano, K., Higashiyama, S., Iwasaka, T. Kidney Int. (2002) [Pubmed]
  38. Divide, accumulate, differentiate: cell condensation in skeletal development revisited. Hall, B.K., Miyake, T. Int. J. Dev. Biol. (1995) [Pubmed]
  39. Steel factor and c-kit regulate cell-matrix adhesion. Kinashi, T., Springer, T.A. Blood (1994) [Pubmed]
  40. Deletion of the alternatively spliced fibronectin EIIIA domain in mice reduces atherosclerosis. Tan, M.H., Sun, Z., Opitz, S.L., Schmidt, T.E., Peters, J.H., George, E.L. Blood (2004) [Pubmed]
  41. Maspin plays an essential role in early embryonic development. Gao, F., Shi, H.Y., Daughty, C., Cella, N., Zhang, M. Development (2004) [Pubmed]
  42. Abnormalities of basement membrane on blood vessels and endothelial sprouts in tumors. Baluk, P., Morikawa, S., Haskell, A., Mancuso, M., McDonald, D.M. Am. J. Pathol. (2003) [Pubmed]
  43. Assembly of exogenous fibronectin by fibronectin-null cells is dependent on the adhesive substrate. Bae, E., Sakai, T., Mosher, D.F. J. Biol. Chem. (2004) [Pubmed]
  44. A null mutation for tissue inhibitor of metalloproteinases-3 (Timp-3) impairs murine bronchiole branching morphogenesis. Gill, S.E., Pape, M.C., Khokha, R., Watson, A.J., Leco, K.J. Dev. Biol. (2003) [Pubmed]
  45. Role of stem cell factor and c-kit signaling in regulation of fetal intestinal epithelial cell adhesion to fibronectin. Shimizu, M., Minakuchi, K., Tsuda, A., Hiroi, T., Tanaka, N., Koga, J., Kiyono, H. Exp. Cell Res. (2001) [Pubmed]
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