TY - JOUR
T1 - NTAL phosphorylation is a pivotal link between the signaling cascades leading to human mast cell degranulation following Kit activation and FcεRI aggregation
AU - Tkaczyk, Christine
AU - Horejsi, Vaclav
AU - Iwaki, Shoko
AU - Draber, Petr
AU - Samelson, Lawrence E.
AU - Satterthwaite, Anne B.
AU - Nahm, Dong Ho
AU - Metcalfe, Dean D.
AU - Gilfillan, Alasdair M.
PY - 2004/7/1
Y1 - 2004/7/1
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2003-08-2769
DO - 10.1182/blood-2003-08-2769
M3 - Article
C2 - 15010370
AN - SCOPUS:3042830452
SN - 0006-4971
VL - 104
SP - 207
EP - 214
JO - Blood
JF - Blood
IS - 1
ER -