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Gene Review

SLA  -  Src-like-adaptor

Homo sapiens

Synonyms: SLA1, SLAP, SLAP-1, SLAP1, Src-like-adapter, ...
 
 
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Disease relevance of SLA

  • Antibodies to a soluble liver antigen/liver pancreas (SLA/LP) appear to be highly specific for the diagnosis of autoimmune hepatitis [1].
  • SLA class I and the induction of SLA class II antigen in response to interferon-gamma treatment were reduced in cells infected with adeno-I(kappa)B(alpha) and empty adenovirus, demonstrating that viral infection alone can influence EC biology [2].
  • MG63 osteoblast-like osteosarcoma cells were cultured on commercially pure Ti disks with various surface roughnesses: pretreatment (PT; 0.6 microm average roughness [Ra]), coarse grit-blasted and acid-etched (SLA; 4 microm RA), and titanium plasma-sprayed (TPS; 5.2-microm R(a)) [3].
  • Following the determination of cytokine producing mononuclear cell populations in response to total Leishmania antigen (SLA), and to the recombinant antigen LACK, correlation analysis were performed between specific cytokine producing populations to identify models for cellular mechanisms of immunoregulation in human cutaneous leishmaniasis [4].
  • CONCLUSIONS: Our preliminary data suggest that combined 99mTc-labeled colloid and vital blue-dye techniques are feasible for SLA detection in endometrial cancer; they represent a very promising tool to transform the management of early-stage endometrial cancer [5].
 

High impact information on SLA

  • The molecular adapter Fyb/Slap regulates signaling downstream of the T cell receptor (TCR), but whether it plays a positive or negative role is controversial [6].
  • In addition to known regulators of antigen receptor signaling, we identified a novel adaptor protein, SLAP-2 which shares 36% sequence similarity with the known Src-like adaptor protein, SLAP [7].
  • Recently the adapter protein ADAP/Fyb/Slap has been shown to couple TCR stimulation to integrin activation by mediating increased integrin avidity [8].
  • The haplotype specificity of SLA, its anther-specific expression, and its physical linkage to the S locus are properties expected for a gene that encodes a determinant of S2 specificity in pollen [9].
  • This gene, which we designated SLA (for S Locus Anther), is a novel gene with an unusual structure [9].
 

Biological context of SLA

 

Anatomical context of SLA

 

Associations of SLA with chemical compounds

  • This molecule lacks a catalytic tyrosine kinase domain and is related to a previously identified protein, Src-like adapter protein (SLAP), and is therefore designated SLAP-2 [19].
  • Expression of Src-like adapter protein mRNA is induced by all-trans retinoic acid [13].
  • Additionally, we have cloned and sequenced approximately 2.6 kb of the region 5' to the initiator methionine of the murine Slap gene [11].
  • There was a twofold increase in PGE2 levels in the media of MG63 cells cultured on glass and PT in response to 14 dynes/cm(2), but on SLA and TPS, 14 dynes/cm(2) shear force caused a 9-10-fold increase [20].
  • Primary female human osteoblasts were cultured to confluence on three Ti surfaces (pretreatment, PT - R(a) 0.60 microm; sandblasted and acid-etched, SLA - R(a) 3.97 microm; and Ti plasma-sprayed, TPS - R(a) 5.21 microm) and treated for 24 h with 10(-7) or 10(-8) M 17beta-estradiol (E(2)) [21].
 

Other interactions of SLA

  • We used an in vitro system consisting of purified VCAM-1/Fc fusion protein or fibronectin immobilized on porous polycarbonate membranes to quantitatively measure the migration efficiency of an Epstein-Barr virus-transformed B cell line (SLA) and T lymphoblasts derived from normal donors [18].
  • One cluster enclosed three class I related genes (SLA-6 to -8) and two genes (MIC-1 and MIC-2) more distantly related to class I. The other cluster enclosed typical class I genes, of which three (SLA-1, -2, and -3) were transcribed by fibroblasts homozygous for the H01 haplotype which we used to construct a pig BAC library [22].
 

Analytical, diagnostic and therapeutic context of SLA

  • In this study, we describe the molecular cloning and characterization of a Src-like adaptor protein gene embedded within the genomic organization of the human thyroglobulin (Tg) gene [23].
  • CONCLUSIONS: Antibodies to SLA/LP can be reliably detected by these standardised immunoassays based on recombinant antigen [24].
  • A formal backcross study was therefore performed in which offspring of (cd x ddR) matings (designated cdbc and ddbc) were bilaterally nephrectomized and transplanted with SLA-matched renal allografts [25].
  • AIH type 3 may be distinguished by autoantibodies to soluble liver proteins (SLA) or the liver pancreas antigen (LP) [26].
  • In contrast, the subset of dd animals which were the product of continuous homozygous matings since establishment of the dd herd (ddR) accepted SLA-matched grafts indefinitely without any immunosuppression [25].

References

  1. A bioinformatical approach suggests the function of the autoimmune hepatitis target antigen soluble liver antigen/liver pancreas. Kernebeck, T., Lohse, A.W., Grötzinger, J. Hepatology (2001) [Pubmed]
  2. Adenoviral-mediated overexpression of I(kappa)B(alpha) in endothelial cells inhibits natural killer cell-mediated endothelial cell activation. Goodman, D.J., von Albertini, M.A., McShea, A., Wrighton, C.J., Bach, F.H. Transplantation (1996) [Pubmed]
  3. Osteoblast response to titanium surface roughness and 1alpha,25-(OH)(2)D(3) is mediated through the mitogen-activated protein kinase (MAPK) pathway. Schwartz, Z., Lohmann, C.H., Vocke, A.K., Sylvia, V.L., Cochran, D.L., Dean, D.D., Boyan, B.D. J. Biomed. Mater. Res. (2001) [Pubmed]
  4. Antigen specific correlations of cellular immune responses in human leishmaniasis suggests mechanisms for immunoregulation. Antonelli, L.R., Dutra, W.O., Almeida, R.P., Bacellar, O., Gollob, K.J. Clin. Exp. Immunol. (2004) [Pubmed]
  5. Preliminary study of sentinel node identification with 99mTc colloid and blue dye in patients with endometrial cancer. Pelosi, E., Arena, V., Baudino, B., Bellò, M., Gargiulo, T., Giusti, M., Bottero, A., Leo, L., Armellino, F., Palladin, D., Bisi, G. Tumori. (2002) [Pubmed]
  6. Positive regulation of T cell activation and integrin adhesion by the adapter Fyb/Slap. Griffiths, E.K., Krawczyk, C., Kong, Y.Y., Raab, M., Hyduk, S.J., Bouchard, D., Chan, V.S., Kozieradzki, I., Oliveira-Dos-Santos, A.J., Wakeham, A., Ohashi, P.S., Cybulsky, M.I., Rudd, C.E., Penninger, J.M. Science (2001) [Pubmed]
  7. Functional cloning of Src-like adapter protein-2 (SLAP-2), a novel inhibitor of antigen receptor signaling. Holland, S.J., Liao, X.C., Mendenhall, M.K., Zhou, X., Pardo, J., Chu, P., Spencer, C., Fu, A., Sheng, N., Yu, P., Pali, E., Nagin, A., Shen, M., Yu, S., Chan, E., Wu, X., Li, C., Woisetschlager, M., Aversa, G., Kolbinger, F., Bennett, M.K., Molineaux, S., Luo, Y., Payan, D.G., Mancebo, H.S., Wu, J. J. Exp. Med. (2001) [Pubmed]
  8. Communication between the TCR and integrins: role of the molecular adapter ADAP/Fyb/Slap. Griffiths, E.K., Penninger, J.M. Curr. Opin. Immunol. (2002) [Pubmed]
  9. An anther-specific gene encoded by an S locus haplotype of Brassica produces complementary and differentially regulated transcripts. Boyes, D.C., Nasrallah, J.B. Plant Cell (1995) [Pubmed]
  10. Chromosomal localization of the mouse Src-like adapter protein (Slap) gene and its putative human homolog SLA. Angrist, M., Wells, D.E., Chakravarti, A., Pandey, A. Genomics (1995) [Pubmed]
  11. Characterization of promoter region and genomic structure of the murine and human genes encoding Src like adapter protein. Kratchmarova, I., Sosinowski, T., Weiss, A., Witter, K., Vincenz, C., Pandey, A. Gene (2001) [Pubmed]
  12. Characterization of human gene encoding SLA/LP autoantigen and its conserved homologs in mouse, fish, fly, and worm. Wang, C.X., Teufel, A., Cheruti, U., Grötzinger, J., Galle, P.R., Lohse, A.W., Herkel, J. World J. Gastroenterol. (2006) [Pubmed]
  13. Expression of Src-like adapter protein mRNA is induced by all-trans retinoic acid. Ohtsuki, T., Hatake, K., Ikeda, M., Tomizuka, H., Terui, Y., Uwai, M., Miura, Y. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  14. Functional cooperation between c-Cbl and Src-like adaptor protein 2 in the negative regulation of T-cell receptor signaling. Loreto, M.P., Berry, D.M., McGlade, C.J. Mol. Cell. Biol. (2002) [Pubmed]
  15. Cutting edge: Dexamethasone negatively regulates Syk in mast cells by up-regulating SRC-like adaptor protein. Hiragun, T., Peng, Z., Beaven, M.A. J. Immunol. (2006) [Pubmed]
  16. Molecular cloning, expression, and chromosomal assignment of sarcolemmal-associated proteins. A family of acidic amphipathic alpha-helical proteins associated with the membrane. Wigle, J.T., Demchyshyn, L., Pratt, M.A., Staines, W.A., Salih, M., Tuana, B.S. J. Biol. Chem. (1997) [Pubmed]
  17. Effects of implant surface microtopography on osteoblast gene expression. Masaki, C., Schneider, G.B., Zaharias, R., Seabold, D., Stanford, C. Clinical oral implants research. (2005) [Pubmed]
  18. VLA-4 integrin mediates lymphocyte migration on the inducible endothelial cell ligand VCAM-1 and the extracellular matrix ligand fibronectin. Chan, P.Y., Aruffo, A. J. Biol. Chem. (1993) [Pubmed]
  19. A novel Src homology 2 domain-containing molecule, Src-like adapter protein-2 (SLAP-2), which negatively regulates T cell receptor signaling. Pandey, A., Ibarrola, N., Kratchmarova, I., Fernandez, M.M., Constantinescu, S.N., Ohara, O., Sawasdikosol, S., Lodish, H.F., Mann, M. J. Biol. Chem. (2002) [Pubmed]
  20. Shear force modulates osteoblast response to surface roughness. Bannister, S.R., Lohmann, C.H., Liu, Y., Sylvia, V.L., Cochran, D.L., Dean, D.D., Boyan, B.D., Schwartz, Z. J. Biomed. Mater. Res. (2002) [Pubmed]
  21. Response of normal female human osteoblasts (NHOst) to 17beta-estradiol is modulated by implant surface morphology. Lohmann, C.H., Tandy, E.M., Sylvia, V.L., Hell-Vocke, A.K., Cochran, D.L., Dean, D.D., Boyan, B.D., Schwartz, Z. J. Biomed. Mater. Res. (2002) [Pubmed]
  22. Spatial arrangement of pig MHC class I sequences. Velten, F.W., Renard, C., Rogel-Gaillard, C., Vaiman, M., Chardon, P. Immunogenetics (1999) [Pubmed]
  23. The gene for the human Src-like adaptor protein (hSLAP) is located within the 64-kb intron of the thyroglobulin gene. Meijerink, P.H., Yanakiev, P., Zorn, I., Grierson, A.J., Bikker, H., Dye, D., Kalaydjieva, L., Baas, F. Eur. J. Biochem. (1998) [Pubmed]
  24. Establishment of standardised SLA/LP immunoassays: specificity for autoimmune hepatitis, worldwide occurrence, and clinical characteristics. Baeres, M., Herkel, J., Czaja, A.J., Wies, I., Kanzler, S., Cancado, E.L., Porta, G., Nishioka, M., Simon, T., Daehnrich, C., Schlumberger, W., Galle, P.R., Lohse, A.W. Gut (2002) [Pubmed]
  25. Transplantation in miniature swine. X. Evidence for non-SLA-linked immune response gene(s) controlling rejection of SLA-matched kidney allografts. Pennington, L.R., Flye, M.W., Kirkman, R.L., Thistlethwaite, J.R., Williams, G.M., Sachs, D.H. Transplantation (1981) [Pubmed]
  26. Autoimmune hepatitis. Obermayer-Straub, P., Strassburg, C.P., Manns, M.P. J. Hepatol. (2000) [Pubmed]
 
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