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Gene Review

Igbp1  -  immunoglobulin (CD79A) binding protein 1

Mus musculus

Synonyms: AI115586, AI662457, AW208785, Alpha4 phosphoprotein, C81413, ...
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Disease relevance of Igbp1

  • We studied the structure and the molecular mechanism of the expression of alpha 4 gene by isolating two phage clones, named #10 and #23, covering entire exons of the mouse alpha 4 gene [1].
  • In contrast with resting LNC, preactivated LNC or alpha 4 beta 7hi lymphoma cells require only alpha 4 beta 7 for arrest in PP-HEV [2].
  • LFA-1-dependent arrest was also abolished by pertussis toxin, implicating a requirement for G alpha i--protein-linked signaling. alpha 4 integrins, which play a critical role in lymphocyte homing to Peyer's Patches, made no significant contribution to attachment, rolling, or sticking in resting PLNs [3].
  • Therapeutic treatment with anti-L-selectin after the onset of insulitis from 10 to 14 weeks of age delayed the onset but failed to prevent spontaneous insulin-dependent diabetes mellitus, whereas anti-integrin alpha 4 treatment resulted in a significant and long-lasting suppression of the disease [4].
  • These data explain why alpha-3 and alpha-4 were not affected by the three independently induced deletion-type mutations that cause alpha-thalassemia in the mouse [5].

High impact information on Igbp1


Chemical compound and disease context of Igbp1

  • Interestingly, the administration of Abs specific for the alpha 4 integrin also highly reduced anti-GBM Ab synthesis, thus preventing detectable glomerular deposits and proteinuria [8].
  • Prevention of mercuric chloride-induced nephritis in the brown Norway rat by treatment with antibodies against the alpha 4 integrin [8].
  • The immunodominant Db-restricted CTL epitope, located at LCMV glycoprotein amino acids 278 to 286, was earlier noted to be recognized by TCRs that consistently contained V alpha 4 segments but had heterogeneous V beta segments [9].
  • In the first, a baby hamster kidney cell line was transfected with the DNA of a plasmid containing the neomycin phosphotransferase gene that confers resistance to the antibiotic G418 and the gene specifying a temperature-sensitive (ts-) alpha 4 protein of HSV-1, the major viral regulatory protein [10].
  • alpha 4 beta 2 subunit combination specific pharmacology of neuronal nicotinic acetylcholine receptors in N1E-115 neuroblastoma cells [11].

Biological context of Igbp1


Anatomical context of Igbp1


Associations of Igbp1 with chemical compounds

  • An in vitro kinase reaction analysis demonstrated that the p52 is tightly associated with the tyrosine kinase molecule(s), one of which is an 80-kDa protein containing an apparent autophosphorylation activity [15].
  • Identification of a 52-kDa molecule (p52) coprecipitated with the Ig receptor-related MB-1 protein that is inducibly phosphorylated by the stimulation with phorbol myristate acetate [15].
  • Compared to normal B cells, alpha 4(-) B cells showed a decreased proliferation in response to the B cell stimulants (anti-IgM antibody plus IL-4, anti-CD40 mAb and lipopolysaccharide), and a reduced S6 kinase activation and rapamycin sensitivity [16].
  • In contrast, alpha 4 (CD49d) integrins are shown here to initiate lymphocyte contract ("tethering") in vitro under shear and in the absence of a selectin contribution [6].
  • Phenotypic characterization of an alpha 4 neuronal nicotinic acetylcholine receptor subunit knock-out mouse [17].

Physical interactions of Igbp1

  • We have modeled peptides based on the predicted structure of the alpha 4 beta 7 integrin binding motif on MAdCAM-1 and are able to show specific and selective blocking of cell binding [18].
  • The adhesion component induced by TNF alpha is mediated by alpha 4-integrins since enhanced binding could be blocked by an antibody against mouse alpha 4 (lymphocyte-Peyer's patch adhesion molecule 1/2) [19].

Regulatory relationships of Igbp1

  • These experiments indicated that c-kit inhibited the transcription of the beta 7 and Fc epsilon RI genes while enhancing alpha 4 transcript levels [20].
  • These results imply that alpha 4 integrins and their ligands could be important for migration or differentiation of neural crest. alpha 4 was also expressed on embryonic retina and FN was found on inductive mesenchyme surrounding the eye, suggesting a role for these proteins in eye development [21].
  • VCAM-1 is a cytokine-inducible cell surface protein capable of mediating adhesion to leukocytes expressing alpha 4 integrins [22].
  • A full-length cDNA coding for the murine alpha 4 integrin subunit (alpha 4m) was transfected into CHO-K1 cells and cell lines that expressed VLA-4 at their surface as a result of the association of transfected alpha 4m with endogenous hamster beta 1 were selected [23].
  • The RA-induced expression of alpha 3 transcripts accounts for a comparably small number of nAChR-containing cells (< 20%) of which half coexpress alpha 4 transcripts [24].

Other interactions of Igbp1


Analytical, diagnostic and therapeutic context of Igbp1


  1. The gene structure and promoter analysis of mouse lymphocyte signal transduction molecule alpha 4 that is related to the yeast TAP42 involved in a rapamycin-sensitive pathway. Maeda, K., Inui, S., Sanjo, H., Sakaguchi, N. Gene (1998) [Pubmed]
  2. Distinct roles of L-selectin and integrins alpha 4 beta 7 and LFA-1 in lymphocyte homing to Peyer's patch-HEV in situ: the multistep model confirmed and refined. Bargatze, R.F., Jutila, M.A., Butcher, E.C. Immunity (1995) [Pubmed]
  3. Molecular mechanisms of lymphocyte homing to peripheral lymph nodes. Warnock, R.A., Askari, S., Butcher, E.C., von Andrian, U.H. J. Exp. Med. (1998) [Pubmed]
  4. A predominant role of integrin alpha 4 in the spontaneous development of autoimmune diabetes in nonobese diabetic mice. Yang, X.D., Michie, S.A., Tisch, R., Karin, N., Steinman, L., McDevitt, H.O. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  5. Mouse alpha-globin genes and alpha-globin-like pseudogenes are not syntenic. Popp, R.A., Lalley, P.A., Whitney, J.B., Anderson, W.F. Proc. Natl. Acad. Sci. U.S.A. (1981) [Pubmed]
  6. alpha 4 integrins mediate lymphocyte attachment and rolling under physiologic flow. Berlin, C., Bargatze, R.F., Campbell, J.J., von Andrian, U.H., Szabo, M.C., Hasslen, S.R., Nelson, R.D., Berg, E.L., Erlandsen, S.L., Butcher, E.C. Cell (1995) [Pubmed]
  7. 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]
  8. Prevention of mercuric chloride-induced nephritis in the brown Norway rat by treatment with antibodies against the alpha 4 integrin. Molina, A., Sánchez-Madrid, F., Bricio, T., Martín, A., Barat, A., Alvarez, V., Mampaso, F. J. Immunol. (1994) [Pubmed]
  9. Diversity of T-cell receptors in virus-specific cytotoxic T lymphocytes recognizing three distinct viral epitopes restricted by a single major histocompatibility complex molecule. Yanagi, Y., Tishon, A., Lewicki, H., Cubitt, B.A., Oldstone, M.B. J. Virol. (1992) [Pubmed]
  10. Construction and properties of a cell line constitutively expressing the herpes simplex virus glycoprotein B dependent on functional alpha 4 protein synthesis. Arsenakis, M., Hubenthal-Voss, J., Campadelli-Fiume, G., Pereira, L., Roizman, B. J. Virol. (1986) [Pubmed]
  11. alpha 4 beta 2 subunit combination specific pharmacology of neuronal nicotinic acetylcholine receptors in N1E-115 neuroblastoma cells. Zwart, R., Abraham, D., Oortgiesen, M., Vijverberg, H.P. Brain Res. (1994) [Pubmed]
  12. Molecular cloning of a cDNA clone encoding a phosphoprotein component related to the Ig receptor-mediated signal transduction. Inui, S., Kuwahara, K., Mizutani, J., Maeda, K., Kawai, T., Nakayasu, H., Sakaguchi, N. J. Immunol. (1995) [Pubmed]
  13. Surface expression of alpha 4 integrin by CD4 T cells is required for their entry into brain parenchyma. Baron, J.L., Madri, J.A., Ruddle, N.H., Hashim, G., Janeway, C.A. J. Exp. Med. (1993) [Pubmed]
  14. Alpha 6 integrins are required for Langerhans cell migration from the epidermis. Price, A.A., Cumberbatch, M., Kimber, I., Ager, A. J. Exp. Med. (1997) [Pubmed]
  15. Identification of a 52-kDa molecule (p52) coprecipitated with the Ig receptor-related MB-1 protein that is inducibly phosphorylated by the stimulation with phorbol myristate acetate. Kuwahara, K., Matsuo, T., Nomura, J., Igarashi, H., Kimoto, M., Inui, S., Sakaguchi, N. J. Immunol. (1994) [Pubmed]
  16. BCR signal through alpha 4 is involved in S6 kinase activation and required for B cell maturation including isotype switching and V region somatic hypermutation. Inui, S., Maeda, K., Hua, D.R., Yamashita, T., Yamamoto, H., Miyamoto, E., Aizawa, S., Sakaguchi, N. Int. Immunol. (2002) [Pubmed]
  17. Phenotypic characterization of an alpha 4 neuronal nicotinic acetylcholine receptor subunit knock-out mouse. Ross, S.A., Wong, J.Y., Clifford, J.J., Kinsella, A., Massalas, J.S., Horne, M.K., Scheffer, I.E., Kola, I., Waddington, J.L., Berkovic, S.F., Drago, J. J. Neurosci. (2000) [Pubmed]
  18. Mucosal addressin cell adhesion molecule-1: a structural and functional analysis demarcates the integrin binding motif. Viney, J.L., Jones, S., Chiu, H.H., Lagrimas, B., Renz, M.E., Presta, L.G., Jackson, D., Hillan, K.J., Lew, S., Fong, S. J. Immunol. (1996) [Pubmed]
  19. Dissection of murine lymphocyte-endothelial cell interaction mechanisms by SV-40-transformed mouse endothelial cell lines: novel mechanisms mediating basal binding, and alpha 4-integrin-dependent cytokine-induced adhesion. Harder, R., Uhlig, H., Kashan, A., Schütt, B., Duijvestijn, A., Butcher, E.C., Thiele, H.G., Hamann, A. Exp. Cell Res. (1991) [Pubmed]
  20. Modulation of integrin expression during mast cell differentiation. Ducharme, L.A., Weis, J.H. Eur. J. Immunol. (1992) [Pubmed]
  21. Expanding roles for alpha 4 integrin and its ligands in development. Sheppard, A.M., Onken, M.D., Rosen, G.D., Noakes, P.G., Dean, D.C. Cell Adhes. Commun. (1994) [Pubmed]
  22. Defective development of the embryonic and extraembryonic circulatory systems in vascular cell adhesion molecule (VCAM-1) deficient mice. Kwee, L., Baldwin, H.S., Shen, H.M., Stewart, C.L., Buck, C., Buck, C.A., Labow, M.A. Development (1995) [Pubmed]
  23. Stable expression of VLA-4 and increased maturation of the beta 1-integrin precursor after transfection of CHO cells with alpha 4m cDNA. Jaspers, M., de Meirsman, C., Schollen, E., Vekemans, S., Cassiman, J.J. FEBS Lett. (1994) [Pubmed]
  24. Nicotinic receptor subunits alpha 3, alpha 4, and beta 2 and high affinity nicotine binding sites are expressed by P19 embryonal cells. Cauley, K., Marks, M., Gahring, L.C., Rogers, S.W. J. Neurobiol. (1996) [Pubmed]
  25. Cell adhesion events mediated by alpha 4 integrins are essential in placental and cardiac development. Yang, J.T., Rayburn, H., Hynes, R.O. Development (1995) [Pubmed]
  26. The Peyer's patch high endothelial receptor for lymphocytes, the mucosal vascular addressin, is induced on a murine endothelial cell line by tumor necrosis factor-alpha and IL-1. Sikorski, E.E., Hallmann, R., Berg, E.L., Butcher, E.C. J. Immunol. (1993) [Pubmed]
  27. Antigen-independent processes in antigen-specific immunity. A role for alpha 4 integrin. Ferguson, T.A., Kupper, T.S. J. Immunol. (1993) [Pubmed]
  28. Acquisition of an intracisternal A-particle element by a translocated c-myc gene in a murine plasma cell tumor. Greenberg, R., Hawley, R., Marcu, K.B. Mol. Cell. Biol. (1985) [Pubmed]
  29. Production of DNP-specific/class I MHC-restricted suppressor molecules is linked to the expression of T cell receptor alpha- and beta-chain genes. Fairchild, R.L., Palmer, E., Moorhead, J.W. J. Immunol. (1993) [Pubmed]
  30. The 170-kDa glucose-regulated stress protein is an endoplasmic reticulum protein that binds immunoglobulin. Lin, H.Y., Masso-Welch, P., Di, Y.P., Cai, J.W., Shen, J.W., Subjeck, J.R. Mol. Biol. Cell (1993) [Pubmed]
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