Be. Szente et al., IDENTIFICATION OF IFN-GAMMA RECEPTOR-BINDING SITES FOR JAK2 AND ENHANCEMENT OF BINDING BY IFN-GAMMA AND ITS C-TERMINAL PEPTIDE IFN-GAMMA(95-133), The Journal of immunology, 155(12), 1995, pp. 5617-5622
The tyrosine kinase jAK2 is an integral part of the signal transductio
n pathways of a number of cytokines and growth factors, including IFN-
gamma. previously, we identified a species-nonspecific binding site fo
r the C terminus of IFN-gamma, encompassed by lFN-gamma peptide IFN-ga
mma(95-133), on the membrane proximal region of the cytoplasmic domain
of the lFN-gamma R alpha-chain. Using both a radioligand binding assa
y and coimmunoprecipitation with antireceptor antiserum, we were able
to demonstrate specific interaction of JAK2 with the murine IFN-gamma
R (MIR) cu-chain. Furthermore, this interaction is increased by the ad
dition of murine IFN-gamma or its C-terminal peptide, mulFN-gamma(95-1
33). We also identified two regions of the cytoplasmic domain of the r
eceptor that interact with JAK2 using synthetic peptides of the MIR al
pha-chain in receptor competition studies. These regions are encompass
ed by receptor peptide MIR(283-309), which is adjacent to the membrane
proximal region at which the C terminus of IFN-gamma binds, and recep
tor peptide MIR(404-432), which lies near the C terminus of the recept
or, encompassing a potentially important phosphorylation site. These d
ata show site-specific interaction between JAK2 and IFN-gamma with the
IFN-gamma R and have broader implications for the role of the IFN-gam
ma ligand in the IFN-gamma signal transduction pathway. Furthermore, t
he data support previous studies that demonstrated that intracellular
lFN-gamma plays a role in cell activation.