Han Xiao PhD thesis - Research@StAndrews:FullText - University of ...

Jak1, allows the docking of STAT1. After STATs dock on specific phosphotyrosines on
the receptor, the Jaks phosphorylate them, phosphorylated STATs dissociated from
receptor and form heterodimer via their Src Homology 2 (SH2) domain. The STAT1-
STAT2 complex associates with a monomer of IRF-9 to form the ISG factor 3 (ISGF3)
heterotrimer complex, translocates to the nucleus, and binds to IFN-stimulated response
element (ISRE) located in the promoter region of most ISGs, thereby initiating their
transcription (Fig. 1.3).
1.1.2.2 Type II IFN signalling
Signalling in response to IFN-γ follows very similar features to that in response to type I
IFN. The IFN-γ receptor is also a heterodimeric glycoprotein, comprising at least two
major subunits, IFNGR1 and IFNGR2 [reviewed by (Bach, Aguet, and Schreiber, 1997)].
In contrast to the type I receptor, the cytoplasmic domains of IFNGR1 and IFNGR2 are
associated with a different set of JAKs, Jak1 and Jak2, respectively. Dimeric IFN-γ
binding to the receptor subunits triggers receptor dimerization and activation of receptor
associated Jak1 and Jak2, which subsequently phosphorylate a tyrosine residue (Y440) on
IFNGR1 that serves as a docking site for STAT1 [Reviewed in (Bach, Aguet, and
Schreiber, 1997)]. STAT1 is then activated by phosphorylation at tyrosine 701, resulting
in the homo-dimerization of STAT1 and dissociation from the receptor. Dimerized
STAT1s translocate to the nucleus and bind to gamma-activation sequence (GAS) that is
present in the promoter region of certain ISGs (Fig. 1.3).
Of the hundreds of known ISGs, some have either a GAS or ISRE elements in their
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