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Blood, 1 December 2006, Vol. 108, No. 12, pp. 3761-3768. Prepublished online as a Blood First Edition Paper on August 15, 2006; DOI 10.1182/blood-2006-02-005397. This Article Full Text (PDF) All Versions of this Article: blood-2006-02-005397v1 108/12/3761    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Grabbe, A. Articles by Wienands, J. Search for Related Content PubMed PubMed Citation Articles by Grabbe, A. Articles by Wienands, J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 23, 2006 Accepted July 25, 2006 Human SLP-65 isoforms contribute differently to activation and apoptosis of B lymphocytes Annika Grabbe and Jurgen Wienands* Georg-August University of Gottingen,Institute of Cellular & Molecular Immunology, Gottingen,Germany * Corresponding author; email: jwienan{at}gwdg.de. The SH2 domain-containing leukocyte adaptor protein of 65 kDa (SLP-65) is the key effector for signaling downstream of the B cell antigen receptor. SLP-65 controls not only B lymphopoiesis and humoral immunity but also possesses a yet poorly defined tumor suppressor activity that is lost in many cases of acute lymphoblastic leukemia. We now found that the two isoforms of human SLP-65 are differentially involved in positive and negative B cell signaling. Reconstitution experiments revealed that an atypical SH3 domain-binding motif, which is present in the long but not in the short SLP-65 isoform, mediates association to Grb2 and suppresses activation of mitogen-activated protein kinases p38 and JNK as well as upregulation of c-Fos expression. In turn, the short isoform activates AP1- but also NF-B-driven gene transcription more potently than the long isoform. Conversely, the long rather than the short SLP-65 isoform promotes BCR-induced B cell apoptosis. Our data further delineate the structural requirements of positive and negative SLP-65 signal transduction in normal and neoplastic cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Oellerich, M. Gronborg, K. Neumann, H.-H. Hsiao, H. Urlaub, and J. Wienands SLP-65 Phosphorylation Dynamics Reveals a Functional Basis for Signal Integration by Receptor-proximal Adaptor Proteins Mol. Cell. Proteomics, July 1, 2009; 8(7): 1738 - 1750. [Abstract] [Full Text] [PDF] N. Gupta, J. Delrow, A. Drawid, A. M. Sengupta, G. Fan, and C. Gelinas Repression of B-Cell Linker (BLNK) and B-Cell Adaptor for Phosphoinositide 3-Kinase (BCAP) Is Important for Lymphocyte Transformation by Rel Proteins Cancer Res., February 1, 2008; 68(3): 808 - 814. [Abstract] [Full Text] [PDF] A. Abudula, A. Grabbe, M. Brechmann, C. Polaschegg, N. Herrmann, I. Goldbeck, K. Dittmann, and J. Wienands SLP-65 Signal Transduction Requires Src Homology 2 domain-mediated Membrane Anchoring and a Kinase-independent Adaptor Function of Syk J. Biol. Chem., September 28, 2007; 282(39): 29059 - 29066. [Abstract] [Full Text] [PDF]

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