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NTAL phosphorylation is a pivotal link between the signaling cascades leading to human mast cell degranulation following Kit activation and Fc epsilon RI aggregation.

Tkaczyk, C; Horejsi, V; Iwaki, S; Draber, P; Samelson, LE; Satterthwaite, AB; Nahm, DH; Metcalfe, DD; Gilfillan, AM
Blood, 104(1):207-214, 2004
Journal Title
Aggregation of high-affinity receptors for immunoglobulin E (Fc epsilon RI) on the surface of mast cells results in degranulation, a response that is potentiated by binding of stem cell factor (SCF) to its receptor Kit. We observed that one of the major initial signaling events associated with Fc epsilon RI-mediated activation of human mast cells (HuMCs) is the rapid tyrosine phosphorylation of a protein of 25 to 30 kDa. The phosphorylation of this protein was also observed in response to SCF. This protein was identified as non-T-cell activation linker (NTAL), an adaptor molecule similar to linker for activated T cells (LAT). Unlike the Fc epsilon RI response, SCF induced NTAL phosphorylation in the absence of detectable LAT phosphorylation. When SCF and antigen were added concurrently, there was a marked synergistic effect on NTAL phosphorylation, however, SCF did not enhance the phosphorylation of LAT induced by Fc epsilon RI aggregation. Fc epsilon RI- and SCF-mediated NTAL phosphorylation appear to be differentially regulated by Src kinases and/or Kit kinase, respectively. Diminution of NTAL expression by silencing RNA oligonucleotides in HuMCs resulted in a reduction of both Kit- and Fc epsilon RI-mediated degranulation. NTAL, thus, appears to be an important link between the signaling pathways that are initiated by these receptors, culminating in mast cell degranulation.
MeSH terms
*Adaptor Proteins, Signal TransducingAnimalsAntigens/metabolismCarrier Proteins/biosynthesisCell Degranulation/*physiologyCell LineEnzyme ActivationEnzyme Inhibitors/pharmacologyHumansMast Cells/*physiologyMembrane Proteins/biosynthesisMicePhosphoproteins/biosynthesisPhosphorylationProteins/immunology/*metabolismProto-Oncogene Proteins c-kit/*metabolismPyrimidines/pharmacologyRNA, Small Interfering/pharmacologyReceptors, IgE/immunology/*metabolismSignal TransductionStem Cell Factor/immunology/metabolismStilbenes/pharmacologyTyrosine/metabolismsrc-Family Kinases/antagonists & inhibitors
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Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
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남, 동호
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