SLP76 and SLP65: complex regulation of signalling in lymphocytes and beyond (original) (raw)

• Clark, S. G., Stern, M. J. & Horvitz, H. R. C. elegans cell-signalling gene sem-5 encodes a protein with SH2 and SH3 domains. Nature 356, 340–344 (1992). Together with references 2 and 3, this study describes the consequences of GRB2 deficiency, the first adaptor protein to be identified.
  CAS PubMed Google Scholar
• Lowenstein, E. J. et al. The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signalling. Cell 70, 431–442 (1992).
  CAS PubMed Google Scholar
• Olivier, J. P. et al. A Drosophila SH2–SH3 adaptor protein implicated in coupling the sevenless tyrosine kinase to an activator of Ras guanine nucleotide exchange, Sos. Cell 73, 179–191 (1993).
  CAS PubMed Google Scholar
• Schlessinger, J. How receptor tyrosine kinases activate Ras. Trends Biochem. Sci. 18, 273–275 (1993).
  CAS PubMed Google Scholar
• Clements, J. L., Ross-Barta, S. E., Tygrett, L. T., Waldschmidt, T. J. & Koretzky, G. A. SLP-76 expression is restricted to hemopoietic cells of monocyte, granulocyte, and T lymphocyte lineage and is regulated during T cell maturation and activation. J. Immunol. 161, 3880–3889 (1998).
  CAS PubMed Google Scholar
• Su, Y. W. & Jumaa, H. LAT links the pre-BCR to calcium signalling. Immunity 19, 295–305 (2003).
  CAS PubMed Google Scholar
• Jumaa, H. et al. Abnormal development and function of B lymphocytes in mice deficient for the signalling adaptor protein SLP-65. Immunity 11, 547–554 (1999).
  CAS PubMed Google Scholar
• Jackman, J. K. et al. Molecular cloning of SLP-76, a 76-kDa tyrosine phosphoprotein associated with Grb2 in T cells. J. Biol. Chem. 270, 7029–7032 (1995).
  CAS PubMed Google Scholar
• Fu, C., Turck, C. W., Kurosaki, T. & Chan, A. C. BLNK: a central linker protein in B cell activation. Immunity 9, 93–103 (1998).
  CAS PubMed Google Scholar
• Gangi-Peterson, L. et al. bca: an activation-related B-cell gene. Mol. Immunol. 35, 55–63 (1998).
  CAS PubMed Google Scholar
• Goitsuka, R. et al. BASH, a novel signalling molecule preferentially expressed in B cells of the bursa of Fabricius. J. Immunol. 161, 5804–5808 (1998).
  CAS PubMed Google Scholar
• Wienands, J. et al. SLP-65: a new signalling component in B lymphocytes which requires expression of the antigen receptor for phosphorylation. J. Exp. Med. 188, 791–795 (1998).
  CAS PubMed PubMed Central Google Scholar
• Bonilla, F. A., Fujita, R. M., Pivniouk, V. I., Chan, A. C. & Geha, R. S. Adapter proteins SLP-76 and BLNK both are expressed by murine macrophages and are linked to signalling via Fcγ receptors I and II/III. Proc. Natl Acad. Sci. USA 97, 1725–1730 (2000).
  CAS PubMed PubMed Central Google Scholar
• Zamoyska, R. et al. The influence of the Src-family kinases, Lck and Fyn, on T cell differentiation, survival and activation. Immunol. Rev. 191, 107–118 (2003).
  CAS PubMed Google Scholar
• Wardenburg, J. B. et al. Phosphorylation of SLP-76 by the ZAP-70 protein-tyrosine kinase is required for T-cell receptor function. J. Biol. Chem. 271, 19641–19644 (1996).
  CAS Google Scholar
• Zhang, W., Sloan-Lancaster, J., Kitchen, J., Trible, R. P. & Samelson, L. E. LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation. Cell 92, 83–92 (1998).
  CAS PubMed Google Scholar
• Jordan, M. S., Singer, A. L. & Koretzky, G. A. Adaptors as central mediators of signal transduction in immune cells. Nature Immunol. 4, 110–116 (2003).
  CAS Google Scholar
• Abraham, R. T. & Weiss, A. Jurkat T cells and development of the T-cell receptor signalling paradigm. Nature Rev. Immunol. 4, 301–308 (2004).
  CAS Google Scholar
• Motto, D. G., Ross, S. E., Wu, J., Hendricks-Taylor, L. R. & Koretzky, G. A. Implication of the GRB2-associated phosphoprotein SLP-76 in T cell receptor-mediated interleukin 2 production. J. Exp. Med. 183, 1937–1943 (1996).
  CAS PubMed Google Scholar
• Yablonski, D., Kuhne, M. R., Kadlecek, T. & Weiss, A. Uncoupling of nonreceptor tyrosine kinases from PLC-g1 in an SLP-76-deficient T cell. Science 281, 413–416 (1998).
  CAS PubMed Google Scholar
• Raab, M., da Silva, A. J., Findell, P. R. & Rudd, C. E. Regulation of Vav-SLP-76 binding by ZAP-70 and its relevance to TCR ζ/CD3 induction of interleukin-2. Immunity 6, 155–164 (1997).
  CAS PubMed Google Scholar
• Onodera, H., Motto, D. G., Koretzky, G. A. & Rothstein, D. M. Differential regulation of activation-induced tyrosine phosphorylation and recruitment of SLP-76 to Vav by distinct isoforms of the CD45 protein-tyrosine phosphatase. J. Biol. Chem. 271, 22225–22230 (1996).
  CAS PubMed Google Scholar
• Tuosto, L., Michel, F. & Acuto, O. p95vav associates with tyrosine-phosphorylated SLP-76 in antigen-stimulated T cells. J. Exp. Med. 184, 1161–1166 (1996).
  CAS PubMed Google Scholar
• Wu, J., Motto, D. G., Koretzky, G. A. & Weiss, A. Vav and SLP-76 interact and functionally cooperate in IL-2 gene activation. Immunity 4, 593–602 (1996).
  CAS PubMed Google Scholar
• Bubeck Wardenburg, J. et al. Regulation of PAK activation and the T cell cytoskeleton by the linker protein SLP-76. Immunity 9, 607–616 (1998).
  CAS PubMed Google Scholar
• Wunderlich, L., Farago, A., Downward, J. & Buday, L. Association of Nck with tyrosine-phosphorylated SLP-76 in activated T lymphocytes. Eur. J. Immunol. 29, 1068–1075 (1999).
  CAS PubMed Google Scholar
• Shim, E. K. et al. Association of the Src homology 2 domain-containing leukocyte phosphoprotein of 76 kD (SLP-76) with the p85 subunit of phosphoinositide 3-kinase. FEBS Lett. 575, 35–40 (2004).
  CAS PubMed Google Scholar
• Su, Y. W. et al. Interaction of SLP adaptors with the SH2 domain of Tec family kinases. Eur. J. Immunol. 29, 3702–3711 (1999).
  CAS PubMed Google Scholar
• Bunnell, S. C. et al. Biochemical interactions integrating Itk with the T cell receptor-initiated signalling cascade. J. Biol. Chem. 275, 2219–2230 (2000).
  CAS PubMed Google Scholar
• Liu, S. K., Fang, N., Koretzky, G. A. & McGlade, C. J. The hematopoietic-specific adaptor protein Gads functions in T-cell signalling via interactions with the SLP-76 and LAT adaptors. Curr. Biol. 9, 67–75 (1999).
  CAS PubMed Google Scholar
• Liu, Q., et al. Structural basis for the specific binding of the Gads SH3 domain to an RxxK motif-containing SLP-76 peptide: a novel mode of peptide recognition. Mol. Cell 11, 471–481 (2003). This study identifies a unique SH3 binding motif present in SLP76 that mediates interaction with GADS.
  CAS PubMed Google Scholar
• Yablonski, D., Kadlecek, T. & Weiss, A. Identification of a phospholipase C-γ1 (PLC-γ1) SH3 domain-binding site in SLP-76 required for T-cell receptor-mediated activation of PLC-γ1 and NFAT. Mol. Cell. Biol. 21, 4208–4218 (2001).
  CAS PubMed PubMed Central Google Scholar
• Sanzenbacher, R., Kabelitz, D. & Janssen, O. SLP-76 binding to p56lck: a role for SLP-76 in CD4-induced desensitization of the TCR/CD3 signalling complex. J. Immunol. 163, 3143–3152 (1999).
  CAS PubMed Google Scholar
• da Silva, A. J. et al. Cloning of a novel T-cell protein FYB that binds FYN and SH2-domain-containing leukocyte protein 76 and modulates interleukin 2 production. Proc. Natl Acad. Sci. USA 94, 7493–7498 (1997).
  CAS PubMed PubMed Central Google Scholar
• Musci, M. A. et al. Molecular cloning of SLAP-130, an SLP-76-associated substrate of the T cell antigen receptor-stimulated protein tyrosine kinases. J. Biol. Chem. 272, 11674–11677 (1997).
  CAS PubMed Google Scholar
• Sauer, K. et al. Hematopoietic progenitor kinase 1 associates physically and functionally with the adaptor proteins B cell linker protein and SLP-76 in lymphocytes. J. Biol. Chem. 276, 45207–45216 (2001).
  CAS PubMed Google Scholar
• Fang, N., Motto, D. G., Ross, S. E. & Koretzky, G. A. Tyrosines 113, 128, and 145 of SLP-76 are required for optimal augmentation of NFAT promoter activity. J. Immunol. 157, 3769–3773 (1996).
  CAS PubMed Google Scholar
• Takata, M. & Kurosaki, T. A role for Bruton's tyrosine kinase in B cell antigen receptor-mediated activation of phospholipase C-γ2. J. Exp. Med. 184, 31–40 (1996).
  CAS PubMed Google Scholar
• Martelli, M. P., Lin, H., Zhang, W., Samelson, L. E. & Bierer, B. E. Signalling via LAT (linker for T-cell activation) and Syk/ZAP70 is required for ERK activation and NFAT transcriptional activation following CD2 stimulation. Blood 96, 2181–2190 (2000).
  CAS PubMed Google Scholar
• Ching, K. A. et al. TCR/CD3-Induced activation and binding of Emt/Itk to linker of activated T cell complexes: requirement for the Src homology 2 domain. J. Immunol. 165, 256–262 (2000).
  CAS PubMed Google Scholar
• Zhang, W. et al. Association of Grb2, Gads, and phospholipase C-γ1 with phosphorylated LAT tyrosine residues. Effect of LAT tyrosine mutations on T cell antigen receptor-mediated signalling. J. Biol. Chem. 275, 23355–23361 (2000).
  CAS PubMed Google Scholar
• Reynolds, L. F. et al. Vav1 transduces T cell receptor signals to the activation of phospholipase C-γ1 via phosphoinositide 3-kinase-dependent and-independent pathways. J. Exp. Med. 195, 1103–1114 (2002).
  CAS PubMed PubMed Central Google Scholar
• Dombroski, D. et al. Kinase-independent functions for Itk in TCR-induced regulation of Vav and the actin cytoskeleton. J. Immunol. 174, 1385–1392 (2005).
  CAS PubMed Google Scholar
• Bokoch, G. M. et al. Interaction of the Nck adapter protein with p21-activated kinase (PAK1). J. Biol. Chem. 271, 25746–25749 (1996).
  CAS PubMed Google Scholar
• Galisteo, M. L., Chernoff, J., Su, Y. C., Skolnik, E. Y. & Schlessinger, J. The adaptor protein Nck links receptor tyrosine kinases with the serine-threonine kinase Pak1. J. Biol. Chem. 271, 20997–21000 (1996).
  CAS PubMed Google Scholar
• Lu, W., Katz, S., Gupta, R. & Mayer, B. J. Activation of Pak by membrane localization mediated by an SH3 domain from the adaptor protein Nck. Curr. Biol. 7, 85–94 (1997).
  CAS PubMed Google Scholar
• Rivero-Lezcano, O. M., Marcilla, A., Sameshima, J. H. & Robbins, K. C. Wiskott-Aldrich syndrome protein physically associates with Nck through Src homology 3 domains. Mol. Cell. Biol. 15, 5725–5731 (1995).
  CAS PubMed PubMed Central Google Scholar
• Zeng, R. et al. SLP-76 coordinates Nck-dependent Wiskott-Aldrich syndrome protein recruitment with Vav-1/Cdc42-dependent Wiskott-Aldrich syndrome protein activation at the T cell-APC contact site. J. Immunol. 171, 1360–1368 (2003).
  CAS PubMed Google Scholar
• Ku, G. M., Yablonski, D., Manser, E., Lim, L. & Weiss, A. A PAK1-PIX-PKL complex is activated by the T-cell receptor independent of Nck, Slp-76 and LAT. EMBO J. 20, 457–465 (2001).
  CAS PubMed PubMed Central Google Scholar
• Phee, H., Abraham, R. T. & Weiss, A. Dynamic recruitment of PAK1 to the immunological synapse is mediated by PIX independently of SLP-76 and Vav1. Nature Immunol. 6, 608–617 (2005).
  CAS Google Scholar
• Berry, D. M., Nash, P., Liu, S. K., Pawson, T. & McGlade, C. J. A high-affinity Arg-X-X-Lys SH3 binding motif confers specificity for the interaction between Gads and SLP-76 in T cell signalling. Curr. Biol. 12, 1336–1341 (2002).
  CAS PubMed Google Scholar
• Singer, A. L. et al. Roles of the proline-rich domain in SLP-76 subcellular localization and T cell function. J. Biol. Chem. 279, 15481–15490 (2004).
  CAS PubMed Google Scholar
• Gonen, R., Beach, D., Ainey, C. & Yablonski, D. T cell receptor-induced activation of phospholipase C-γ1 depends on a sequence-independent function of the P-I region of SLP-76. J. Biol. Chem. 280, 8364–8370 (2005).
  CAS PubMed Google Scholar
• Hashimoto, S. et al. Identification of the SH2 domain binding protein of Bruton's tyrosine kinase as BLNK — functional significance of Btk-SH2 domain in B-cell antigen receptor-coupled calcium signalling. Blood 94, 2357–2364 (1999).
  CAS PubMed Google Scholar
• Fusaki, N. et al. BLNK is associated with the CD72/SHP-1/Grb2 complex in the WEHI231 cell line after membrane IgM crosslinking. Eur. J. Immunol. 30, 1326–1330 (2000).
  CAS PubMed Google Scholar
• Ishiai, M., Sugawara, H., Kurosaki, M. & Kurosaki, T. Cutting edge: association of phospholipase C-γ2 Src homology 2 domains with BLNK is critical for B cell antigen receptor signalling. J. Immunol. 163, 1746–1749 (1999).
  CAS PubMed Google Scholar
• Ishiai, M. et al. BLNK required for coupling Syk to PLC γ2 and Rac1-JNK in B cells. Immunity 10, 117–125 (1999).
  CAS PubMed Google Scholar
• Rodriguez, R., Matsuda, M., Storey, A. & Katan, M. Requirements for distinct steps of phospholipase Cγ2 regulation, membrane-raft-dependent targeting and subsequent enzyme activation in B-cell signalling. Biochem. J. 374, 269–280 (2003).
  CAS PubMed PubMed Central Google Scholar
• Pappu, R. et al. Requirement for B cell linker protein (BLNK) in B cell development. Science 286, 1949–1954 (1999). This study, together with references 91, 92, 115 and 116, describes the generation of SLP65- and SLP76-deficient mice.
  CAS PubMed Google Scholar
• Tan, J. E., Wong, S. C., Gan, S. K., Xu, S. & Lam, K. P. The adaptor protein BLNK is required for B cell antigen receptor-induced activation of nuclear factor-κB and cell cycle entry and survival of B lymphocytes. J. Biol. Chem. 276, 20055–20063 (2001).
  CAS PubMed Google Scholar
• Fujikawa, K. et al. Vav1/2/3-null mice define an essential role for Vav family proteins in lymphocyte development and activation but a differential requirement in MAPK signalling in T and B cells. J. Exp. Med. 198, 1595–1608 (2003).
  CAS PubMed PubMed Central Google Scholar
• Johmura, S. et al. Regulation of Vav localization in membrane rafts by adaptor molecules Grb2 and BLNK. Immunity 18, 777–787 (2003). Together with reference 64, this study shows the importance of SLP76 and SLP65 in the localization of other signal-transduction molecules.
  CAS PubMed Google Scholar
• Wu, J. N. & Koretzky, G. A. The SLP-76 family of adapter proteins. Semin. Immunol. 16, 379–393 (2004).
  CAS PubMed Google Scholar
• Charvet, C., Canonigo, A. J., Billadeau, D. D. & Altman, A. Membrane localization and function of Vav3 in T cells depend on its association with the adapter SLP-76. J. Biol. Chem. 280, 15289–15299 (2005).
  CAS PubMed Google Scholar
• Simons, K. & Toomre, D. Lipid rafts and signal transduction. Nature Rev. Mol. Cell Biol. 1, 31–39 (2000).
  CAS Google Scholar
• Samelson, L. E. Signal transduction mediated by the T cell antigen receptor: the role of adapter proteins. Annu. Rev. Immunol. 20, 371–394 (2002).
  CAS PubMed Google Scholar
• Boerth, N. J. et al. Recruitment of SLP-76 to the membrane and glycolipid-enriched membrane microdomains replaces the requirement for linker for activation of T cells in T cell receptor signalling. J. Exp. Med. 192, 1047–1058 (2000).
  CAS PubMed PubMed Central Google Scholar
• Bunnell, S. C. et al. T cell receptor ligation induces the formation of dynamically regulated signalling assemblies. J. Cell Biol. 158, 1263–1275 (2002). In this study, the authors investigate the temporal and spatial localization of proximal signalling molecules and highlight the potential of use of microscopy for investigation of these important aspects of signalling.
  CAS PubMed PubMed Central Google Scholar
• Wong, J., Ishiai, M., Kurosaki, T. & Chan, A. C. Functional complementation of BLNK by SLP-76 and LAT linker proteins. J. Biol. Chem. 275, 33116–33122 (2000).
  CAS PubMed Google Scholar
• Pierce, S. K. Lipid rafts and B-cell activation. Nature Rev. Immunol. 2, 96–105 (2002).
  CAS Google Scholar
• Dykstra, M., Cherukuri, A., Sohn, H. W., Tzeng, S. J. & Pierce, S. K. Location is everything: lipid rafts and immune cell signalling. Annu. Rev. Immunol. 21, 457–481 (2003).
  CAS PubMed Google Scholar
• Janssen, E., Zhu, M., Zhang, W. & Koonpaew, S. LAB: a new membrane-associated adaptor molecule in B cell activation. Nature Immunol. 4, 117–123 (2003).
  CAS Google Scholar
• Brdicka, T. et al. Non-T cell activation linker (NTAL): a transmembrane adaptor protein involved in immunoreceptor signalling. J. Exp. Med. 196, 1617–1626 (2002).
  CAS PubMed PubMed Central Google Scholar
• Wang, Y. et al. Single and combined deletions of the NTAL/LAB and LAT adaptors minimally affect B-cell development and function. Mol. Cell. Biol. 25, 4455–4465 (2005).
  CAS PubMed PubMed Central Google Scholar
• Ishiai, M. et al. Involvement of LAT, Gads, and Grb2 in compartmentation of SLP-76 to the plasma membrane. J. Exp. Med. 192, 847–856 (2000).
  CAS PubMed PubMed Central Google Scholar
• Engels, N., Wollscheid, B. & Wienands, J. Association of SLP-65/BLNK with the B cell antigen receptor through a non-ITAM tyrosine of Ig-α. Eur. J. Immunol. 31, 2126–2134 (2001).
  CAS PubMed Google Scholar
• Kabak, S. et al. The direct recruitment of BLNK to immunoglobulin-α couples the B-cell antigen receptor to distal signalling pathways. Mol. Cell. Biol. 22, 2524–2535 (2002).
  CAS PubMed PubMed Central Google Scholar
• Kohler, F. et al. A leucine zipper in the N terminus confers membrane association to SLP-65. Nature Immunol. 6, 204–210 (2005). This study identifies a newly identified mechanism for SLP65 recruitment to the plasma membrane, which potentially explains the dispensability of LAT and NTAL to SLP65 function.
  Google Scholar
• Munro, S. Lipid rafts: elusive or illusive? Cell 115, 377–388 (2003).
  CAS PubMed Google Scholar
• Lichtenberg, D., Goni, F. M. & Heerklotz, H. Detergent-resistant membranes should not be identified with membrane rafts. Trends Biochem. Sci. 30, 430–436 (2005).
  CAS PubMed Google Scholar
• Zhu, M., Shen, S., Liu, Y., Granillo, O. & Zhang, W. Cutting Edge: Localization of linker for activation of T cells to lipid rafts is not essential in T cell activation and development. J. Immunol. 174, 31–35 (2005).
  CAS PubMed Google Scholar
• Douglass, A. D. & Vale, R. D. Single-molecule microscopy reveals plasma-membrane microdomains created by protein-protein networks that exclude or trap signalling molecules in T cells. Cell 121, 937–950 (2005). A technically powerful study indicates that the key regulator of plasma-membrane microdomains is protein-interaction networks as opposed to lipid rafts.
  CAS PubMed PubMed Central Google Scholar
• Chiu, C. W., Dalton, M., Ishiai, M., Kurosaki, T. & Chan, A. C. BLNK: molecular scaffolding through 'cis'-mediated organization of signalling proteins. EMBO J. 21, 6461–6472 (2002).
  CAS PubMed PubMed Central Google Scholar
• Houtman, J. C. et al. Binding specificity of multiprotein signalling complexes is determined by both cooperative interactions and affinity preferences. Biochemistry 43, 4170–4178 (2004). Results from this study indicate that interaction with multiple binding partners by a single SLP65 molecule is required for function.
  CAS PubMed Google Scholar
• Ladbury, J. E. & Arold, S. Searching for specificity in SH domains. Chem. Biol. 7, R3–R8 (2000).
  CAS PubMed Google Scholar
• Obergfell, A. et al. The molecular adapter SLP-76 relays signals from platelet integrin αΙΙbβ3 to the actin cytoskeleton. J. Biol. Chem. 276, 5916–5923 (2001).
  CAS PubMed Google Scholar
• Newbrough, S. A. et al. SLP-76 regulates Fcγ receptor and integrin signalling in neutrophils. Immunity 19, 761–769 (2003).
  PubMed Google Scholar
• Obergfell, A. et al. Coordinate interactions of Csk, Src, and Syk kinases with αΙΙbβ3 initiate integrin signalling to the cytoskeleton. J. Cell Biol. 157, 265–275 (2002).
  CAS PubMed PubMed Central Google Scholar
• Inoue, O., Suzuki-Inoue, K., Dean, W. L., Frampton, J. & Watson, S. P. Integrin α2β1 mediates outside-in regulation of platelet spreading on collagen through activation of Src kinases and PLCγ2. J. Cell Biol. 160, 769–780 (2003).
  CAS PubMed PubMed Central Google Scholar
• Judd, B. A. et al. Differential requirement for LAT and SLP-76 in GPVI versus T cell receptor signalling. J. Exp. Med. 195, 705–717 (2002).
  CAS PubMed PubMed Central Google Scholar
• Clements, J. L. et al. Requirement for the leukocyte-specific adapter protein SLP-76 for normal T cell development. Science 281, 416–419 (1998).
  CAS PubMed Google Scholar
• Pivniouk, V. et al. Impaired viability and profound block in thymocyte development in mice lacking the adaptor protein SLP-76. Cell 94, 229–238 (1998).
  CAS PubMed Google Scholar
• Aifantis, I. et al. Allelic exclusion of the T cell receptor-β locus requires the SH2 domain-containing leukocyte protein (SLP)-76 adaptor protein. J. Exp. Med. 190, 1093–1102 (1999).
  CAS PubMed PubMed Central Google Scholar
• Myung, P. S. et al. Differential requirement for SLP-76 domains in T cell development and function. Immunity 15, 1011–1026 (2001). This study identifies a requirement for SLP76 in thymocyte development past the DN3 stage and proves that lineage-specific SLP76 deletion, and possibly temporally controlled SLP76 deletion, is feasible for the study of SLP76 function at later stages in thymocyte development.
  CAS PubMed Google Scholar
• Kumar, L., Pivniouk, V., de la Fuente, M. A., Laouini, D. & Geha, R. S. Differential role of SLP-76 domains in T cell development and function. Proc. Natl Acad. Sci. USA 99, 884–889 (2002).
  CAS PubMed PubMed Central Google Scholar
• Maltzman, J. S., Kovoor, L., Clemens, J. L. & Koretzky, G. A. Conditional deletion of SLP-76 reveals a cell autonomous requirement for thymocyte selection. J. Exp. Med. 202, 893–900 (2005).
  CAS PubMed PubMed Central Google Scholar
• Jouvin, M. H. et al. Differential control of the tyrosine kinases Lyn and Syk by the two signalling chains of the high affinity immunoglobulin E receptor. J. Biol. Chem. 269, 5918–5925 (1994).
  CAS PubMed Google Scholar
• Hendricks-Taylor, L. R., Motto, D. G., Zhang, J., Siraganian, R. P. & Koretzky, G. A. SLP-76 is a substrate of the high affinity IgE receptor-stimulated protein tyrosine kinases in rat basophilic leukemia cells. J. Biol. Chem. 272, 1363–1367 (1997).
  CAS PubMed Google Scholar
• Pivniouk, V. I. et al. SLP-76 deficiency impairs signalling via the high-affinity IgE receptor in mast cells. J. Clin. Invest. 103, 1737–1743 (1999).
  CAS PubMed PubMed Central Google Scholar
• Kettner, A. et al. Structural requirements of SLP-76 in signalling via the high-affinity immunoglobulin E receptor (FcεRI) in mast cells. Mol. Cell Biol. 23, 2395–2406 (2003).
  CAS PubMed PubMed Central Google Scholar
• Wu, J. N., Jordan, M. S., Silverman, M. A., Peterson, E. J. & Koretzky, G. A. Differential requirement for adapter proteins Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa and adhesion- and degranulation-promoting adapter protein in FcεRI signalling and mast cell function. J. Immunol. 172, 6768–6774 (2004).
  CAS PubMed Google Scholar
• Parravicini, V. et al. Fyn kinase initiates complementary signals required for IgE-dependent mast cell degranulation. Nature Immunol. 3, 741–748 (2002).
  CAS Google Scholar
• Clements, J. L. et al. Fetal hemorrhage and platelet dysfunction in SLP-76-deficient mice. J. Clin. Invest. 103, 19–25 (1999).
  CAS PubMed PubMed Central Google Scholar
• Gross, B. S. et al. Tyrosine phosphorylation of SLP-76 is downstream of Syk following stimulation of the collagen receptor in platelets. J. Biol. Chem. 274, 5963–5971 (1999).
  CAS PubMed Google Scholar
• Berton, G. Tyrosine kinases in neutrophils. Curr. Opin. Hematol. 6, 51–58 (1999).
  CAS PubMed Google Scholar
• Nichols, K. E. et al. Macrophage activation and Fcγ receptor-mediated signalling do not require expression of the SLP-76 and SLP-65 adaptors. J. Leukoc. Biol. 75, 541–552 (2004).
  CAS PubMed Google Scholar
• Myung, P. S. et al. In vitro and in vivo macrophage function can occur independently of SLP-76. Int. Immunol. 12, 887–897 (2000).
  CAS PubMed Google Scholar
• Cohen-Solal, J. F., Cassard, L., Fridman, W. H. & Sautes-Fridman, C. Fcγ receptors. Immunol. Lett. 92, 199–205 (2004).
  CAS PubMed Google Scholar
• Shivdasani, R. A. et al. Transcription factor NF-E2 is required for platelet formation independent of the actions of thrombopoietin/MGDF in megakaryocyte development. Cell 81, 695–704 (1995).
  CAS PubMed Google Scholar
• Abtahian, F. et al. Regulation of blood and lymphatic vascular separation by signalling proteins SLP-76 and Syk. Science 299, 247–251 (2003). This study reports the intriguing finding that points to a newly discovered role for SLP76 and SYK in regulating lymphatic vessel separation from blood vasculature.
  CAS PubMed PubMed Central Google Scholar
• Cheng, A. M. et al. Syk tyrosine kinase required for mouse viability and B-cell development. Nature 378, 303–306 (1995).
  CAS PubMed Google Scholar
• Turner, M. et al. Perinatal lethality and blocked B-cell development in mice lacking the tyrosine kinase Syk. Nature 378, 298–302 (1995).
  CAS PubMed Google Scholar
• Wang, D. et al. Phospholipase Cγ2 is essential in the functions of B cell and several Fc receptors. Immunity 13, 25–35 (2000).
  PubMed Google Scholar
• Zhang, W. et al. Essential role of LAT in T cell development. Immunity 10, 323–332 (1999).
  CAS PubMed Google Scholar
• Hayashi, K. et al. The B cell-restricted adaptor BASH is required for normal development and antigen receptor-mediated activation of B cells. Proc. Natl Acad. Sci. USA 97, 2755–2760 (2000).
  CAS PubMed PubMed Central Google Scholar
• Xu, S. et al. B cell development and activation defects resulting in _xid_-like immunodeficiency in BLNK/SLP-65-deficient mice. Int. Immunol. 12, 397–404 (2000).
  CAS PubMed Google Scholar
• Xu, S., Wong, S. C. & Lam, K. P. Cutting edge: B cell linker protein is dispensable for the allelic exclusion of immunoglobulin heavy chain locus but required for the persistence of CD5+ B cells. J. Immunol. 165, 4153–4157 (2000).
  CAS PubMed Google Scholar
• Engel, P. et al. Abnormal B lymphocyte development, activation, and differentiation in mice that lack or overexpress the CD19 signal transduction molecule. Immunity 3, 39–50 (1995).
  CAS PubMed Google Scholar
• Rickert, R. C., Rajewsky, K. & Roes, J. Impairment of T-cell-dependent B-cell responses and B-1 cell development in CD19-deficient mice. Nature 376, 352–355 (1995).
  CAS PubMed Google Scholar
• Hayashi, K., Yamamoto, M., Nojima, T., Goitsuka, R. & Kitamura, D. Distinct signalling requirements for Dμ selection, IgH allelic exclusion, pre-B cell transition, and tumour suppression in B cell progenitors. Immunity 18, 825–836 (2003).
  CAS PubMed Google Scholar
• Minegishi, Y. et al. An essential role for BLNK in human B cell development. Science 286, 1954–1957 (1999).
  CAS PubMed Google Scholar
• Conley, M. E., Rohrer, J., Rapalus, L., Boylin, E. C. & Minegishi, Y. Defects in early B-cell development: comparing the consequences of abnormalities in pre-BCR signalling in the human and the mouse. Immunol. Rev. 178, 75–90 (2000).
  CAS PubMed Google Scholar
• Flemming, A., Brummer, T., Reth, M. & Jumaa, H. The adaptor protein SLP-65 acts as a tumour suppressor that limits pre-B cell expansion. Nature Immunol. 4, 38–43 (2003).
  CAS Google Scholar
• Jumaa, H. et al. Deficiency of the adaptor SLP-65 in pre-B-cell acute lymphoblastic leukaemia. Nature 423, 452–456 (2003). This study raises the possibility that SLP65 might function as a tumour suppressor and could potentially be a marker of transformation. A larger study described in reference 125 implies that SLP65 expression might be dysregulated in only a subset of patients with B-cell ALL.
  CAS PubMed Google Scholar
• Imai, C. et al. Expression of the adaptor protein BLNK/SLP-65 in childhood acute lymphoblastic leukemia. Leukemia 18, 922–925 (2004).
  CAS PubMed Google Scholar
• Gerlach, J. et al. B cell defects in SLP65/BLNK-deficient mice can be partially corrected by the absence of CD22, an inhibitory coreceptor for BCR signalling. Eur. J. Immunol. 33, 3418–3426 (2003).
  CAS PubMed Google Scholar
• Mizuno, K., Tagawa, Y., Watanabe, N., Ogimoto, M. & Yakura, H. SLP-76 is recruited to CD22 and dephosphorylated by SHP-1, thereby regulating B cell receptor-induced c-Jun N-terminal kinase activation. Eur. J. Immunol. 35, 644–654 (2005).
  CAS PubMed Google Scholar
• Gerke, C., Falkow, S. & Chien, Y. H. The adaptor molecules LAT and SLP-76 are specifically targeted by Yersinia to inhibit T cell activation. J. Exp. Med. 201, 361–371 (2005).
  CAS PubMed PubMed Central Google Scholar
• Kwon, J. et al. Receptor-stimulated oxidation of SHP-2 promotes T-cell adhesion through SLP-76-ADAP. EMBO J. 24, 2331–2341 (2005).
  CAS PubMed PubMed Central Google Scholar
• Chiang, Y. J. et al. Inactivation of c-Cbl reverses neonatal lethality and T cell developmental arrest of SLP-76-deficient mice. J. Exp. Med. 200, 25–34 (2004).
  CAS PubMed PubMed Central Google Scholar