Omz. Howard et al., STRUCTURAL DOMAINS OF INTERLEUKIN-2 RECEPTOR-BETA CRITICAL FOR SIGNAL-TRANSDUCTION - KINASE ASSOCIATION AND NUCLEAR COMPLEX-FORMATION, Biochemical journal, 306, 1995, pp. 217-224
The structural domains of interleukin-2 receptor beta (IL-2R beta) wer
e examined, characterizing the protein domains, associated phosphoprot
eins and nuclear complexes of IL-2-induced signal transduction. A seri
es of IL-2R beta cytoplasmic deletion mutants were constructed and tra
nsfected into a murine pre-B-cell line, Ba/F3. The proliferative respo
nse of characterized clones was determined. A minimal linear cytoplasm
ic sequence required for proliferation and a sequence motif (PQPLXP) n
eeded along with Box1-Box2 for IL-2-induced proliferation were identif
ied, Anti-phosphotyrosine Western-blot analysis of a stimulated biolog
ically active clone showed several IL-2-induced tyrosylphosphorylated
proteins with molecular masses ranging from 45 to 116 kDa. In vitro ki
nase studies of biologically active clone-receptor complexes showed a
116 kDa protein (p116) to be the major tyrosine-phosphorylated compone
nt. The presence of the p116 kinase in the receptor complex correlates
with IL-2-induced proliferation. An IL-2-inducible p116 kinase has re
cently been characterized as a Jak kinase family member and named Jak3
. Nuclear complexes were formed with the GRR oligomer only when the IL
-2R beta mutant supported proliferation. This led us to conclude that
Box1-Box2 and PQPLXP motifs associate with Jak3 and that this associat
ion is an essential element in the IL-2 signal-transduction pathway cu
lminating in the formation of a nuclear complex.