Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

X-linked lympho-proliferative (XLP) is an immunodeficiency condition caused by mutation or deletion of the gene encoding the adaptor protein SAP/SH2D1A. Besides defects in T cell and NK cell function and an absence of NKT cells, XLP can also manifest as lymphomas resulting primarily from uncontrolled B cell proliferation upon acute infection by Epstein-Barr virus. While it has been demonstrated that SAP regulates the functions of T cells and NK cells through the SLAM family of immunoreceptors, its role in B cells has not been defined. Here we show that SAP forms a ternary complex with the kinase Lyn and the inhibitory IgG Fc receptor FcgammaRIIB to regulate B cell proliferation and survival. SAP binds directly and simultaneously to the Lyn SH3 domain and an Immuno-receptor Tyrosine-based Inhibitory Motif (ITIM) in FcgammaRIIB, resulting in the activation of the latter. Moreover, SAP associates with FcgammaRIIB in mouse splenic B cells and promotes its tyrosine phosphorylation. Expression of SAP in the A20 B cell line led to a marked reduction in Blnk phosphorylation, a decrease in Akt activation, and a near-complete ablation of phosphorylation of the MAP kinases Erk1/2, p38 and JNK upon colligation of FcgammaRIIB with the B cell receptor (BCR). In contrast, an XLP-causing SAP mutant was much less efficient in eliciting these effects in B cells. Furthermore, compared to A20 cells, SAP transfectants displayed a significantly reduced rate of proliferation and an increased sensitivity to activation-induced cell death. Collectively these data identify an intrinsic function for SAP in inhibitory signaling in B cells and suggests that SAP may play an important role in balancing positive versus negative immune responses.
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PMID:The X-linked lymphoproliferative syndrome gene product SAP regulates B cell function through the FcgammaRIIB receptor. 1866 72

The gene sap/shd1a, which encodes a 128-residue SH2 domain protein, is frequently deleted or mutated in the X-linked lymphoproliferative syndrome (XLP). The SAP SH2 domain differs from others in the same class in that it is not only capable of binding to a phosphotyrosine-containing peptide, it can also associate with an SH3 domain using a distinct surface. This novel mode of ligand-binding is initially discovered in the SLAM-SAP-Fyn complex that plays a critical role in T cell and natural killer cell activation. To identify additional binding partners for SAP, we screened a panel of 12 SH3 domains derived from regulatory proteins and identified NCK1 as a novel target of SAP in T cells. NMR analysis demonstrated that the NCK1 and Fyn SH3 domains possessed comparable affinities for SAP and engaged the same set of residues on the surface of the SAP SH2 domain. Depletion of SAP by siRNA caused a significant decrease in NCK1 tyrosine phosphorylation as well as the phosphorylation of other T cell receptor (TCR) downstream proteins such as LAT and SLP-76. Moreover, SAP was shown to regulate T cell proliferation through the MAP-kinase Erk. Taken together, our work identifies NCK1 as a novel physiological partner for SAP and a direct regulator of TCR signaling and T cell proliferation.
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PMID:The XLP syndrome protein SAP interacts with SH3 proteins to regulate T cell signaling and proliferation. 1895 76

The automatic place recognition problem is one of the key challenges in SLAM approaches for loop closure detection. Most of the appearance-based solutions to this problem share the idea of image feature extraction, memorization, and matching search. The weakness of these solutions is the storage and computational costs which increase drastically with the environment size. In this regard, the major constraints to overcome are the required visual information storage and the complexity of similarity computation. In this paper, a novel formulation is proposed that allows the computation time reduction while no visual information are stored and matched explicitly. The proposed solution relies on the incremental building of a bio-inspired visual memory using a Fuzzy ART network. This network considers the properties discovered in primate brain. The performance evaluation of the proposed method has been conducted using two datasets representing different large scale outdoor environments. The method has been compared with RatSLAM and FAB-MAP approaches and has demonstrated a decreased time and storage costs with broadly comparable precision recall performance.
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PMID:Fuzzy ART-based place recognition for visual loop closure detection. 2322 95