34 258

Cited 92 times in

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

Authors
Tkaczyk, C; Horejsi, V; Iwaki, S; Draber, P; Samelson, LE; Satterthwaite, AB; Nahm, DH; Metcalfe, DD; Gilfillan, AM
Citation
Blood, 104(1):207-214, 2004
Journal Title
Blood
ISSN
0006-49711528-0020
Abstract
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
DOI
10.1182/blood-2003-08-2769
PMID
15010370
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
AJOU Authors
남, 동호
Full Text Link
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse