Engagement of the Fcepsilon receptor I (FcepsilonRI) on mast cells and basophils initiates signaling pathways leading to degranulation. Early activation events include tyrosine phosphorylation of two transmembrane adaptor proteins, linker for activation of T cells (LAT) and non-T cell activation linker (NTAL; also called LAB; a product of Wbscr5 gene). Previous studies showed that the secretory response was partially inhibited in bone marrow-derived mast cells (BMMCs) from LAT-deficient mice. To clarify the role of NTAL in mast cell degranulation, we compared FcepsilonRI-mediated signaling events in BMMCs from NTAL-deficient and wild-type mice. Although NTAL is structurally similar to LAT, antigen-mediated degranulation responses were unexpectedly increased in NTAL-deficient mast cells. The earliest event affected was enhanced tyrosine phosphorylation of LAT in antigen-activated cells. This was accompanied by enhanced tyrosine phosphorylation and enzymatic activity of phospholipase C gamma1 and phospholipase C gamma2, resulting in elevated levels of inositol 1,4,5-trisphosphate and free intracellular Ca2+. NTAL-deficient BMMCs also exhibited an enhanced activity of phosphatidylinositol 3-OH kinase and Src homology 2 domain-containing protein tyrosine phosphatase-2. Although both LAT and NTAL are considered to be localized in membrane rafts, immunogold electron microscopy on isolated membrane sheets demonstrated their independent clustering. The combined data show that NTAL is functionally and topographically different from LAT.

• MeSH
• adaptorové proteiny signální transdukční fyziologie   MeSH
• adaptorové proteiny vezikulární transportní fyziologie   MeSH
• degranulace buněk MeSH
• fosfatidylinositol-3-kinasy fyziologie   MeSH
• fosfolipasa C gama MeSH
• fosfolipasy typu C metabolismus   MeSH
• fosfoproteiny fyziologie   MeSH
• fosforylace MeSH
• mastocyty fyziologie   MeSH
• membránové proteiny fyziologie   MeSH
• myši MeSH
• proteiny fyziologie   MeSH
• receptory IgE fyziologie   MeSH
• signální transdukce * MeSH
• tyrosin metabolismus   MeSH
• vápník metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adaptorové proteiny signální transdukční MeSH
• adaptorové proteiny vezikulární transportní MeSH
• fosfolipasa C gama MeSH
• fosfolipasy typu C MeSH
• fosfoproteiny MeSH
• LAB protein, mouse MeSH Prohlížeč
• Lat protein, mouse MeSH Prohlížeč
• LAT2 protein, mouse MeSH Prohlížeč
• membránové proteiny MeSH
• proteiny MeSH
• receptory IgE MeSH
• tyrosin MeSH
• vápník MeSH