Differential associations between the cytoplasmic regions of the interleukin-12 receptor subunits beta1 and beta2 and JAK kinases

• Published in: The Journal of biological chemistry Vol. 272; no. 9; pp. 6073 - 6077
• Main Authors: Zou, J, Presky, D H, Wu, C Y, Gubler, U
• Format: Journal Article
• Language: English
• Published: United States 28.02.1997
• Subjects: Barium Compounds - metabolism; ErbB Receptors - genetics; ErbB Receptors - metabolism; Flow Cytometry; Fluorides - metabolism; Humans; Interleukin-12 - metabolism; Janus Kinase 3; Phosphorylation; Protein Conformation; Protein-Tyrosine Kinases - metabolism; Receptors, Interleukin - chemistry; Receptors, Interleukin - metabolism; Receptors, Interleukin-12; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - metabolism; Tyrosine - metabolism
• ISSN: 0021-9258

The role of the cytoplasmic regions of interleukin-12 receptors (IL-12R) beta1 and beta2 in stimulating proliferation was examined. The transmembrane and cytoplasmic regions of IL-12Rbeta1 or IL-12Rbeta2 were fused to the extracellular domain of the epidermal growth factor (EGF) receptor, yielding chimeric receptors E12R1 and E12R2, respectively. These chimeras were stably transfected into BaF3 cells, a factor-dependent murine pro-B cell line. Only E12R2 or E12R1+E12R2 transfectants were capable of EGF-dependent proliferation. EGF-dependent phosphorylation of E12R2, JAK2, Tyk2, and STAT3 was observed. JAK2 was phosphorylated in E12R1-, E12R2-, and E12R1+E12R2-expressing cells. However, direct associations were detectable only between E12R2 and JAK2. Tyk2 phosphorylation was observed only in cells expressing E12R1 or E12R1+E12R2. In parallel with this activation pattern, direct interactions only between Tyk2 and E12R1 were demonstrable. Phosphorylation of STAT3 was observed in cells expressing E12R1, E12R2, and E12R1+E12R2. The expression levels of STAT4 protein in BaF3 cells are undetectable by the methods employed here; therefore, STAT4 phosphorylation was not observed. Taken together, the data indicate that differential interactions take place between the cytoplasmic regions of the two IL-12R subunits and JAK2/Tyk2 and that the cytoplasmic region of IL-12Rbeta2 alone is capable of delivering a proliferative signal.