The type l interferon receptor belongs to the class II cytokine receptor family and is expressed on all cell types as a heterodimeric complex that consists of the IFNAR1 and IFNAR2 subunits. Binding of interferon a/ß to its receptor triggers phosphorylation of associated tyrosine kinases of Jak family, Tyk2 and Jak1, and subsequent downstream signalling events. Recent findings have shown that Jak protein tyrosine kinases can control cellular responses to cytokines by influencing receptor localization, modulating their surface expression levels, and therefore the formation of functional high affinity receptors.
Based on initial studies with IFNAR1 and Tyk2, which revealed Tyk2 dependent IFNAR1 surface expression, I propose to study the role of Tyk2 in ligand dependent events. I will focus in particular on the potential role ofTyk2 in ligand-dependent IFNAR1 trafficking. A second aspect of the study will take into account IFNAR2 subunit of the type l interferon receptor and its associated tyrosine kinase Jak1. I propose to examine whether IFNAR2 surface expression is Jak1 dependent and to check whether and how does it correlate with expression of IFNAR1.
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