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

• Moreover, alpha 4 beta 7 mediates L-selectin (CD62L)-independent attachment of blood-borne lymphocytes to lamina propria venules in situ [6].
• The alpha 4 integrin ligands MAdCAM-1 and VCAM-1 support loose reversible interactions including rolling, as well as rapid sticking and arrest that is favored following integrin activation [6].
• alpha 4 integrins mediate lymphocyte attachment and rolling under physiologic flow [6].
• Thus, alpha 4 but not beta 2 integrins can initiate leukocyte adhesion under flow, a capacity that may be in part a function of topographic presentation on microvilli [6].
• Lymphoid cells recognize an alternatively spliced segment of fibronectin via the integrin receptor alpha 4 beta 1 [7].

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

• The alpha 4 cDNA encodes a novel protein of 340 amino acids with multiple potential phosphorylation sites [12].
• Immune complex kinase assay with the 19-14 mAb showed that the p52 is associated with a novel kinase molecule and is involved in IgR-mediated signal transduction [12].
• Here we isolated a cDNA clone (alpha 4) from a murine bone marrow cDNA library in lambda gt-11 vector by the 19-14 mAb [12].
• The alpha 4 gene is located within about 25 kb and composed of six exons [1].
• To analyze the regulation of alpha 4 gene expression, we determined the nucleotide sequence toward 2 kb upstream of the translation start site of the alpha 4 gene [1].

Anatomical context of Igbp1

• These results suggested that the alpha 4 gene-encoded molecule is functionally involved in the IgR-mediated signal transduction in B cells [12].
• The 1.4-kb alpha 4 mRNA is expressed in various cells including cell lines of B lineage, T lineage, monocytic, fibroblast, and normal organs such as liver, spleen, thymus, and brain [12].
• A general conclusion of these studies is that alpha 4 integrins may be crucial in allowing activated effector T cells to leave blood and enter the brain and other tissues to clear infections [13].
• In addition, alpha 4 integrins did not affect the accumulation of LCs as DCs in draining lymph nodes [14].
• Encephalitogenic clones and nonencephalitogenic variants differ by 10-fold in their level of surface expression of alpha 4 integrin and in their ability to bind to endothelial cells and recombinant vascular cell adhesion molecule 1 (VCAM-1) [13].

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

• A rat mAb, prepared by immunizing the 52-kDa protein purified from SDS-PAGE, could detect the similar 52-kDa phosphoprotein (p52) expressed on the cell surface [15].
• 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 [16].
• Both processes clearly involve alpha 4 integrin interactions that were previously unsuspected. alpha 4 integrin and VCAM-1 are expressed at the sites of these interactions [25].
• This binding is blocked by the antibodies against MAdCAM-1 and against the alpha 4-chain of its integrin receptor, alpha 4 beta 7, on TK1 cells.(ABSTRACT TRUNCATED AT 400 WORDS)[26]
• Although R1-2 identifies alpha 4 integrin on a large number of T cells, it does not discriminate between activated and resting forms of this integrin, because very few T cells from immune or nonimmune mice actually bind FN or activated endothelium [27].

Analytical, diagnostic and therapeutic context of Igbp1

• In comparison with the 52-kDa protein in the immunoprecipitate of MB-1, the p52 migrated to the same position on 2-D gel electrophoresis (nonequilibrium pH gradient gel electrophoresis/SDS-PAGE) [15].
• Comparative restriction mapping and DNA sequence analyses demonstrated that an intracisternal A-particle (IAP) element inserted approximately 2 kilobases 3' of an alpha 4-type myc gene to generate the alpha 25 gene copy [28].
• Northern blot analyses indicated the absence of the MTs 79.1 V alpha 4 chain transcript in five of the variants and the absence of the parental V beta 8 chain transcript in the other seven [29].
• Using site-directed mutagenesis and molecular modeling, we demarcate the alpha 4 beta 7 binding motif as three linear residues within the C-D loop in the first domain of MAdCAM-1 [18].
• Immunoprecipitation of GRP170 with our antibody coprecipitates the GRP78 (also referred to as the B cell immunoglobulin-binding protein) and GRP94 members of this stress protein family in Chinese hamster ovary cells under stress conditions [30].

References