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

FcεRI aggregation on the surface of mast cells results in degranulation, a response which 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 25-30 kD. 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 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. FcεRIand 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 which are initiated by these receptors culminating in mast cell degranulation. only. For personal use at PENN STATE UNIVERSITY on February 23, 2013. bloodjournal.hematologylibrary.org From