Formation of the immunological synapse between an antigen-presenting cell (APC) and a T cell leads to signal generation in both cells involved. In T cells, the lipid raft-associated transmembrane adaptor protein LAT plays a central role. Its phosphorylation is a crucial step in signal propagation, including the calcium response and mitogen-activated protein kinase activation, and largely depends on its association with the SLP76 adaptor protein. Here we report the discovery of a new palmitoylated transmembrane adaptor protein, termed SCIMP. SCIMP is expressed in B cells and other professional APCs and is localized in the immunological synapse due to its association with tetraspanin-enriched microdomains. In B cells, it is constitutively associated with Lyn kinase and becomes tyrosine phosphorylated after major histocompatibility complex type II (MHC-II) stimulation. When phosphorylated, SCIMP binds to the SLP65 adaptor protein and also to the inhibitory kinase Csk. While the association with SLP65 initiates the downstream signaling cascades, Csk binding functions as a negative regulatory loop. The results suggest that SCIMP is involved in signal transduction after MHC-II stimulation and therefore serves as a regulator of antigen presentation and other APC functions.

• MeSH
• adaptorové proteiny signální transdukční chemie   metabolismus   MeSH
• aktivace lymfocytů MeSH
• antigen prezentující buňky imunologie   MeSH
• B-lymfocyty imunologie   metabolismus   MeSH
• fosfoproteiny metabolismus   MeSH
• HEK293 buňky MeSH
• histokompatibilita - antigeny třídy II imunologie   metabolismus   MeSH
• imunologické synapse chemie   MeSH
• lidé MeSH
• malá interferující RNA MeSH
• membránové mikrodomény chemie   metabolismus   MeSH
• membránové proteiny chemie   genetika   imunologie   metabolismus   MeSH
• mitogenem aktivované proteinkinasy metabolismus   MeSH
• molekulární sekvence - údaje MeSH
• prezentace antigenu MeSH
• RNA interference MeSH
• sekvence aminokyselin MeSH
• signální transdukce MeSH
• skupina kinas odvozených od src-genu metabolismus   MeSH
• src homologní domény MeSH
• T-lymfocyty imunologie   MeSH
• tyrosinkinasy chemie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH