Physical interaction between interleukin-12 receptor beta 2 subunit and Jak2 tyrosine kinase: Jak2 associates with cytoplasmic membrane-proximal region of interleukin-12 receptor beta 2 via amino-terminus

IL-12 is a heterodimeric cytokine, composed of p40 and p35 subunits, that e xerts its biological effects by binding to specific cell surface receptors. Two human IL-12 receptor proteins, designated IL-12R beta 1 and IL-12R bet a 2, have been previously identified. IL-12R beta 2 has box 1 motif, box 2 motif, and three tyrosine residues in its cytoplasmic domain. In response t o IL-12, Jak2 and Tyk2, family members of Janus family protein tyrosine kin ases, are phosphorylated in PHA-activated T lymphocytes. The present study demonstrates that Jak2 binds to the cytoplasmic membrane-proximal region of IL-12R beta 2, and box 2 motif and tyrosine residues in the cytoplasmic do main were not required for binding. The amino-terminus of Jak2 is necessary for association with IL-12R beta 2. (C) 1999 Academic Press.