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

Christine Tkaczyk, Vaclav Horejsi, Shoko Iwaki, Petr Draber, Lawrence E. Samelson, Anne B. Satterthwaite, Dong Ho Nahm, Dean D. Metcalfe, Alasdair M. Gilfillan

Research output: Contribution to journalArticlepeer-review

96 Scopus citations

Abstract

Aggregation of high-affinity receptors for immunoglobulin E (FcεRI) 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 FcεRI-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 FcεRI 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 FcεRI aggregation. FcεRI- 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 FcεRI-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.

Original languageEnglish (US)
Pages (from-to)207-214
Number of pages8
JournalBlood
Volume104
Issue number1
DOIs
StatePublished - Jul 1 2004

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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