Recombinant Mouse IFN-gamma R2 Protein, CF

IFN‑ gamma R2 (Interferon gamma receptor 2; also called IFN‑ gamma R beta IFN‑ gamma RII, or AF1) is a 60‑64 kDa type I transmembrane glycoprotein that is a member of the class II cytokine receptor family of molecules (1). It is widely expressed as part of a preassembled cell surface multimeric complex. In the absence of IFN‑ gamma, the complex contains two each of IFN‑ gamma R1, R2 and Jak1 molecules (2). Binding of IFN‑ gamma to IFN‑ gamma R1 recruits Jak2 to IFN‑ gamma R2 and initiates phosphorylation, STAT1 binding, conformational changes, and transcriptional regulation, which mainly inhibits proliferation and/or promotes apoptosis (2, 3). Mouse IFN‑ gamma R2 cDNA encodes 332 amino acids (aa), including a signal sequence (aa 1‑27), an extracellular region (ECD, aa 28‑243) with two fibronectin type III domains, a transmembrane sequence (aa 244‑264) and a cytoplasmic tail (aa 265-332) (1, 2). Within the ECD, mouse IFN‑ gamma R2 shares 80% aa sequence identity with rat IFN‑ gamma R2, and 49‑55% with human, canine, porcine and bovine IFN‑ gamma R2. IFN‑ gamma R1 and R2 must be from the same species for receptor complexes to be active, and human IFN‑ gamma is not active on the mouse IFN‑ gamma receptor complex (1, 2). IFN‑ gamma R1 is essential for ligand binding and is more constitutively expressed, while IFN‑ gamma R2 is essential for signaling, and its more limited expression controls cell response to IFN‑ gamma (2, 3). For example, mouse T cell IFN‑ gamma R2 is down‑regulated during differentiation to subtypes such as Th1 which produce IFN‑ gamma. (3, 4) This allows expansion of activated cells without growth arrest due to paracrine response to IFN‑ gamma. Following expansion, IFN‑ gamma R2 is re‑expressed to limit the immune reaction (5). IFN‑ gamma signaling mediates control of intracellular pathogens such as mycobacteria (3, 4, 6). In humans, deficiency of IFN‑ gamma R2 or other IFN‑ gamma pathway molecules causes the MSMD (mendelian susceptibility to mycobacterial diseases) syndrome (6‑8).