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http://purl.uniprot.org/citations/14729663http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/14729663http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/14729663http://www.w3.org/2000/01/rdf-schema#comment"Actin cytoskeleton dynamics critically regulate T cell activation. We found that the cytoplasmic adaptor HIP-55, a Src/Syk-kinases substrate and member of the drebrin/Abp1 family of actin-binding proteins, localized to the T cell-antigen-presenting cell (APC) contact site in an antigen-dependent manner. Using green fluorescent protein fusion proteins, both Src homology 3 (SH3) and actin binding domains were found necessary for recruitment at the T cell-APC interface. HIP-55 was not implicated in conjugate formation and actin polymerization but regulated distal signaling events through binding and activation of hematopoietic progenitor kinase 1 (HPK1), a germinal center kinase (GCK) family kinase involved in negative signaling in T cells. Using RNA interference and overexpression experiments, the HIP-55-HPK1 complex was found to negatively regulate nuclear factor of activated T cell (NFAT) activation by the T cell antigen receptor. Moreover, we show that HIP-55, which partly co-localized with early endocytic compartments, promoted both basal and ligand-dependent T cell receptor (TCR) down-modulation, resulting in a decreased TCR expression. SH3 and actin-depolymerizing factor homology domains were required for this function. As controls, the expression of CD28 and the glycosylphosphatidylinositol-linked protein CD59 was not affected by HIP-55 overexpression. These results suggest that, in addition to binding to HPK1, HIP-55 might negatively regulate TCR signaling through down-regulation of TCR expression. Our findings show that HIP-55 is a key novel component of the immunological synapse that modulates T cell activation by connecting actin cytoskeleton and TCRs to gene activation and endocytic processes."xsd:string
http://purl.uniprot.org/citations/14729663http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m312659200"xsd:string
http://purl.uniprot.org/citations/14729663http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m312659200"xsd:string
http://purl.uniprot.org/citations/14729663http://purl.uniprot.org/core/author"Acuto O."xsd:string
http://purl.uniprot.org/citations/14729663http://purl.uniprot.org/core/author"Acuto O."xsd:string
http://purl.uniprot.org/citations/14729663http://purl.uniprot.org/core/author"Foucault I."xsd:string
http://purl.uniprot.org/citations/14729663http://purl.uniprot.org/core/author"Foucault I."xsd:string
http://purl.uniprot.org/citations/14729663http://purl.uniprot.org/core/author"Deckert M."xsd:string
http://purl.uniprot.org/citations/14729663http://purl.uniprot.org/core/author"Deckert M."xsd:string
http://purl.uniprot.org/citations/14729663http://purl.uniprot.org/core/author"Brignone C."xsd:string
http://purl.uniprot.org/citations/14729663http://purl.uniprot.org/core/author"Brignone C."xsd:string
http://purl.uniprot.org/citations/14729663http://purl.uniprot.org/core/author"Foussat A."xsd:string
http://purl.uniprot.org/citations/14729663http://purl.uniprot.org/core/author"Foussat A."xsd:string
http://purl.uniprot.org/citations/14729663http://purl.uniprot.org/core/author"Le Bras S."xsd:string
http://purl.uniprot.org/citations/14729663http://purl.uniprot.org/core/author"Le Bras S."xsd:string
http://purl.uniprot.org/citations/14729663http://purl.uniprot.org/core/date"2004"xsd:gYear
http://purl.uniprot.org/citations/14729663http://purl.uniprot.org/core/date"2004"xsd:gYear
http://purl.uniprot.org/citations/14729663http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/14729663http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/14729663http://purl.uniprot.org/core/pages"15550-15560"xsd:string
http://purl.uniprot.org/citations/14729663http://purl.uniprot.org/core/pages"15550-15560"xsd:string
http://purl.uniprot.org/citations/14729663http://purl.uniprot.org/core/title"Recruitment of the actin-binding protein HIP-55 to the immunological synapse regulates T cell receptor signaling and endocytosis."xsd:string
http://purl.uniprot.org/citations/14729663http://purl.uniprot.org/core/title"Recruitment of the actin-binding protein HIP-55 to the immunological synapse regulates T cell receptor signaling and endocytosis."xsd:string
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