Figure 9
Proposed model of signalling at the IFNγR that control enteric epithelial macromolecular permeability. (a) Ligation of the IFNγR stimulates JAK-dependent phosphorylation of IFNγR1 resulting in rapid STAT1 recruitment and phosphorylation (b) that allows for a JAK-dependent recruitment and phosphorylation of STAT5b at IFNγR2 along with Fyn Src kinase (c). The Gab2 scaffolding protein is recruited to STAT5b and phosphorylated via Fyn, leading to a STAT5b/Gab2 complex that may remain associated with Fyn (d). Within 2–6 h, PI3K (p85 recruitment/regulatory domain and p110 catalytic domain) is recruited to Gab2 (e), and p85 phosphorylation, possibly via Fyn, relieves inhibition of the catalytic subunit (f). The active PI3K is then available to mobilize membrane lipids and a putative host of downstream enzymes that can lead to decreased epithelial barrier function (g). P, phosphorylated residue.
