The non-specific cytotoxic cell receptor (NCCRP-1): molecular organization and signaling properties.
The evolutionary precursor to mammalian natural killer cells in teleost fish is called non-specific cytotoxic cells (NCC). NCC collaborate with other non-specific effector mechanisms to provide innate resistance during acute stress responses. The NCC receptor protein (NCCRP-1) contains 238 amino acid residues and is believed to be a type III membrane protein with three distinct functional domains. The antigen-binding domain has been mapped to amino acids nos. 104-119. The intracellular C-terminus contains a high concentration of potential phosphorylation sites (Y, S, T). Indeed, we have shown that activation of NCC by crosslinking of NCCRP-1 leads to receptor tyrosine and serine phosphorylation. The N-terminus of the molecule is also inside the cells and has as well signature amino acids, proline-rich motifs (PRM), that are indicative of functional relevance. The cytokine/hormone receptor-like PRMs are known docking sites for JAK kinases. We have evidence that following activation, NCCRP-1 comes in contact with JAK kinase and as a result of this interaction, STAT 6 is translocated into the nucleus. These results suggest that NCCRP-1 may play a dual role in the activation of NCC: first, as an antigen recognition molecule necessary for target cell lysis, and second, as an initiator of cytokine release from NCC. Both of these processes are required for a competent innate immune response.
Jaso-Friedmann
L
L
Department of Medical Microbiology and Parasitology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA. ljaso@vet.uga.edu
Leary
J H
JH
Evans
D L
DL
D000595:Amino Acid Sequence; D000818:Animals; D003602:Cytotoxicity, Immunologic; D005399:Fishes / Q000235:genetics / Q000276:immunology*; D008954:Models, Biological; D011946:Receptors, Antigen / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D015533:Transcriptional Activation
D011946:Receptors, Antigen; C110644:nonspecific cytotoxic cell receptor protein 1