Investigation of signal integration by non-catalytic tyrosine phosphorylated receptors in leukocytes (360G-Wellcome-099812_Z_12_Z)

This work will investigate signal integration in cells through analysis of non-catalytic tyrosine-phosphorylated receptors (NTRs). NTRs are a recently described group of leukocyte cell-surface receptors [1, 2] that share a numberof features, including: i) they contain, or associate with adaptor molecules that contain, tyrosine residues that are phosphorylated by extrinsic kinases such as Lck; ii) they have relatively small extracellular domains ( < 20nm); iii) they bind surface-associated ligands. I will focus on analysis of interactions between NTRs containing immunoreceptor tyrosine-based activating motifs (ITAMs) and those containing immunoreceptor tyrosine-based inhibitory motifs (ITIMs). Key goals of the research include: 1) To develop a system for analysis of signal integration at the cell surface 2) To determine whether matched sizes of receptor/ligand pairs are required for signal integration of ITIM- and ITAM-containing receptors 3) To determine the importance of the length of the intracellular tail of ITIM-containing NTRs for inhibitory efficiency