Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51812 (mitogen-activated protein)
 10,636 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunoreceptor tyrosine-based activation motifs (ITAMs) are crucial in antigen receptor signaling in acquired immunity. Although receptors associated with the ITAM-bearing adaptors FcRgamma and DAP12 on myeloid cells have been suggested to activate innate immune responses, the mechanism coupling those receptors to 'downstream' signaling events is unclear. The CARMA1-Bcl-10-MALT1 complex is critical for the activation of transcription factor NF-kappaB in lymphocytes but has an unclear function in myeloid cells. Here we report that deletion of the gene encoding the Bcl-10 adaptor-binding partner CARD9 resulted in impaired myeloid cell activation of NF-kappaB signaling by several ITAM-associated receptors. Moreover, CARD9 was required for Toll-like receptor-induced activation of dendritic cells through the activation of mitogen-activated protein kinases. Although Bcl10-/- and Card9-/- mice had similar signaling impairment in myeloid cells, Card11-/- (CARMA1-deficient) myeloid cell responses were normal, and although Card11-/- lymphocytes were defective in antigen receptor-mediated activation, Card9-/- lymphocytes were not. Thus, the activation of lymphoid and myeloid cells through ITAM-associated receptors or Toll-like receptors is regulated by CARMA1-Bcl-10 and CARD9-Bcl-10, respectively.
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PMID:The adaptor protein CARD9 is essential for the activation of myeloid cells through ITAM-associated and Toll-like receptors. 1751 6

Nuclear factor-kappaB (NF-kappaB) and mitogen-activated protein kinases (MAPKs) are activated upon engagement of a wide variety of immunoreceptors. Accumulating evidence has demonstrated that B-cell lymphoma 10 (BCL10) and mucosa-associated lymphoid tissue (MALT1) are essential signaling components for NF-kappaB and MAPK activation mediated by immunoreceptor tyrosine-based activation motif (ITAM)-coupled receptors in both adaptive and innate immunity. Recent studies have revealed that two caspase-recruitment domain (CARD) family adaptor molecules, CARD-containing MAGUK protein 1 (CARMA1) and CARD9, are crucial regulators of the ITAM-mediated signaling pathway by forming a complex with BCL10-MALT1 in lymphoid and myeloid cells, respectively. Here, we describe the immune responses and the cell-type-specific regulation mechanisms for NF-kappaB and MAPK activation controlled by CARMA1 and CARD9 through innate and adaptive immunoreceptors.
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PMID:CARD9 versus CARMA1 in innate and adaptive immunity. 1935 18