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Gene Review

Fgr  -  Gardner-Rasheed feline sarcoma viral (Fgr)...

Mus musculus

Synonyms: Proto-oncogene c-Fgr, Tyrosine-protein kinase Fgr, p55-Fgr
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Disease relevance of Fgr

  • Resistance to endotoxic shock and reduced neutrophil migration in mice deficient for the Src-family kinases Hck and Fgr [1].
  • These findings suggest that deficiency of Fgr results in a marked reduction of lung eosinophilia and the establishment of a positive feedback loop based on autocrine secretion of eosinophil-active cytokines [2].
  • We have now isolated and mapped three overlapping phage clones spanning 33 kb of the murine C-FGR genomic locus [3].

High impact information on Fgr


Chemical compound and disease context of Fgr

  • Using a mouse model of allergic lung inflammation, we found that mice deficient of Fgr, a Src family tyrosine kinase highly expressed in myelomonocytic cells, fail to develop lung eosinophilia in response to repeated challenge with aerosolized OVA [2].

Biological context of Fgr


Anatomical context of Fgr

  • With an immune complex kinase assay in a monocytic leukemia cell line, 2H2 monoclonal antibody was shown to precipitate a 59-kDa protein that corresponds in molecular mass to murine Fgr [12].
  • Fgr was expressed highly in lymph nodes, slightly in spleen and peripheral blood leukocytes, and barely in the thymus and was not detected in bone marrow [12].
  • In the presence of a mild detergent, Fgr was coimmunoprecipitated with a 70-kDa protein (p70) or with p70 plus several other molecules that were expressed on the cell-surface membrane of macrophage tumor cell lines PU5-1.8 and J774.1, respectively [12].
  • We also show that Fgr, like other B cell kinases, is activated in response to cross-linking of the Ag receptor [13].
  • We chose Fgr because it is present in high concentrations in circulating phagocytes but is not essential for Fcgamma receptor-mediated ingestion by mouse macrophages [7].

Associations of Fgr with chemical compounds


Regulatory relationships of Fgr


Other interactions of Fgr

  • However, lung eosinophilia in Fgr-deficient mice correlated with a defective accumulation of GM-CSF and IL-5 in the airways, whereas secretion of these cytokines by spleen cells in response to OVA was normal [2].
  • This suggests that exposure of platelets to LDL induces association of apoER2' to Fgr, a kinase that is able to activate p38MAPK [17].
  • These results suggest that Fgr is physically and functionally associated with Fc gamma RII and involved in Fc gamma RII-mediated signal transduction pathways [16].
  • Additionally, examination of integrin affinity by soluble ICAM-1 binding assays and of beta(2) integrin clustering on the cell surface, showed that integrin activation did not require Hck and Fgr expression [18].
  • Mutations in the non-catalytic domains of Fyn and Fgr tyrosine kinases reveal differences in mechanisms of their regulation [10].

Analytical, diagnostic and therapeutic context of Fgr


  1. Resistance to endotoxic shock and reduced neutrophil migration in mice deficient for the Src-family kinases Hck and Fgr. Lowell, C.A., Berton, G. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  2. Fgr deficiency results in defective eosinophil recruitment to the lung during allergic airway inflammation. Vicentini, L., Mazzi, P., Caveggion, E., Continolo, S., Fumagalli, L., Lapinet-Vera, J.A., Lowell, C.A., Berton, G. J. Immunol. (2002) [Pubmed]
  3. Isolation and characterization of the murine C-FGR genomic locus: exons IB-XII. Podhipleux, N., Willman, C.L. Oncogene (1995) [Pubmed]
  4. The Src family kinases Hck and Fgr negatively regulate neutrophil and dendritic cell chemokine signaling via PIR-B. Zhang, H., Meng, F., Chu, C.L., Takai, T., Lowell, C.A. Immunity (2005) [Pubmed]
  5. Inhibition of beta 2 integrin receptor and Syk kinase signaling in monocytes by the Src family kinase Fgr. Vines, C.M., Potter, J.W., Xu, Y., Geahlen, R.L., Costello, P.S., Tybulewicz, V.L., Lowell, C.A., Chang, P.W., Gresham, H.D., Willman, C.L. Immunity (2001) [Pubmed]
  6. Fcgamma receptor-mediated phagocytosis in macrophages lacking the Src family tyrosine kinases Hck, Fgr, and Lyn. Fitzer-Attas, C.J., Lowry, M., Crowley, M.T., Finn, A.J., Meng, F., DeFranco, A.L., Lowell, C.A. J. Exp. Med. (2000) [Pubmed]
  7. Negative regulation of phagocytosis in murine macrophages by the Src kinase family member, Fgr. Gresham, H.D., Dale, B.M., Potter, J.W., Chang, P.W., Vines, C.M., Lowell, C.A., Lagenaur, C.F., Willman, C.L. J. Exp. Med. (2000) [Pubmed]
  8. Lipopolysaccharide (LPS)-induced macrophage activation and signal transduction in the absence of Src-family kinases Hck, Fgr, and Lyn. Meng, F., Lowell, C.A. J. Exp. Med. (1997) [Pubmed]
  9. Adhesion-dependent degranulation of neutrophils requires the Src family kinases Fgr and Hck. Mócsai, A., Ligeti, E., Lowell, C.A., Berton, G. J. Immunol. (1999) [Pubmed]
  10. Mutations in the non-catalytic domains of Fyn and Fgr tyrosine kinases reveal differences in mechanisms of their regulation. Rivero-Lezcano, O.M., Marcilla, A., Robbins, K.C. Oncogene (1995) [Pubmed]
  11. The proto-oncogene Fgr regulates cell migration and this requires its plasma membrane localization. Continolo, S., Baruzzi, A., Majeed, M., Caveggion, E., Fumagalli, L., Lowell, C.A., Berton, G. Exp. Cell Res. (2005) [Pubmed]
  12. The murine c-fgr gene product associated with Ly6C and p70 integral membrane protein is expressed in cells of a monocyte/macrophage lineage. Hatakeyama, S., Iwabuchi, K., Ogasawara, K., Good, R.A., Onoé, K. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  13. src-family tyrosine kinase p55fgr is expressed in murine splenic B cells and is activated in response to antigen receptor cross-linking. Wechsler, R.J., Monroe, J.G. J. Immunol. (1995) [Pubmed]
  14. Impaired integrin-mediated signal transduction, altered cytoskeletal structure and reduced motility in Hck/Fgr deficient macrophages. Suen, P.W., Ilic, D., Caveggion, E., Berton, G., Damsky, C.H., Lowell, C.A. J. Cell. Sci. (1999) [Pubmed]
  15. Identification of the Src family kinases, Lck and Fgr in platelets. Their tyrosine phosphorylation status and subcellular distribution compared with other Src family members. Pestina, T.I., Stenberg, P.E., Druker, B.J., Steward, S.A., Hutson, N.K., Barrie, R.J., Jackson, C.W. Arterioscler. Thromb. Vasc. Biol. (1997) [Pubmed]
  16. Association of immunoglobulin G Fc receptor II with Src-like protein-tyrosine kinase Fgr in neutrophils. Hamada, F., Aoki, M., Akiyama, T., Toyoshima, K. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  17. Binding of low density lipoprotein to platelet apolipoprotein E receptor 2' results in phosphorylation of p38MAPK. Korporaal, S.J., Relou, I.A., van Eck, M., Strasser, V., Bezemer, M., Gorter, G., van Berkel, T.J., Nimpf, J., Akkerman, J.W., Lenting, P.J. J. Biol. Chem. (2004) [Pubmed]
  18. The Src family kinases Hck and Fgr are dispensable for inside-out, chemoattractant-induced signaling regulating beta 2 integrin affinity and valency in neutrophils, but are required for beta 2 integrin-mediated outside-in signaling involved in sustained adhesion. Giagulli, C., Ottoboni, L., Caveggion, E., Rossi, B., Lowell, C., Constantin, G., Laudanna, C., Berton, G. J. Immunol. (2006) [Pubmed]
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