2005
DOI: 10.1073/pnas.0501063102
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Implications of an antiparallel dimeric structure of nonphosphorylated STAT1 for the activation–inactivation cycle

Abstract: IFN-␥ treatment of cells leads to tyrosine phosphorylation of signal transducer and activator of transcription (STAT) 1 followed by dimerization through a reciprocal Src homology 2-phosphotyrosine interaction near the -COOH end of each monomer, forming a parallel structure that accumulates in the nucleus to drive transcription. Prompt dephosphorylation and return to the cytoplasm completes the activation-inactivation cycle. Nonphosphorylated STATs dimerize, and a previously described interface between N-termin… Show more

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Cited by 140 publications
(154 citation statements)
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References 30 publications
(37 reference statements)
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“…The ''pocket'' residues Q 340 , Q 408 , and G 384 are required for spatial reorientation of a parallel to an anti-parallel STAT1 dimer presenting the pY 701 to TCP45 (Zhong et al 2005;Mertens et al 2006). It appears feasible that after initial activation, and once acetylated in the nucleus by CBP, STAT1 is stabilized in its anti-parallel structure providing access for TCP45.…”
Section: Discussionmentioning
confidence: 99%
“…The ''pocket'' residues Q 340 , Q 408 , and G 384 are required for spatial reorientation of a parallel to an anti-parallel STAT1 dimer presenting the pY 701 to TCP45 (Zhong et al 2005;Mertens et al 2006). It appears feasible that after initial activation, and once acetylated in the nucleus by CBP, STAT1 is stabilized in its anti-parallel structure providing access for TCP45.…”
Section: Discussionmentioning
confidence: 99%
“…Remarkably, dimerization of STAT1 is not necessary for the initiation of IFN-dependent signaling [33,34]. Moreover, positive and negative transcriptional control can also be exerted by unphosphorylated STAT1 via mechanisms distinct from those used by phosphorylated STAT1 [35][36][37][38].…”
Section: Regulation Of Stat1 Signalingmentioning
confidence: 99%
“…A radical transition from parallel to antiparallel conformation, which allows the presentation of the phosphorylated tyrosine residues of STAT1 dimers to TCP45, has been suggested [34,61]. The existence of multiple layers of temporal and spatial regulation of cytokine-induced signaling allows precise control of genes important for metazoan growth, immune defense and development via STAT1.…”
Section: Regulation Of Stat1 Signalingmentioning
confidence: 99%
“…IFN-γ stimulation leads to activation of the associated Janus kinases JAK1 and JAK2, which phosphorylate the tetrameric IFN-γ receptor, creating a docking site for 2 latent STAT1 molecules. These molecules are phosphorylated on their Tyr701 residues and are released into the cytosol as phosphorylated active STAT1 homodimers, forming gamma-activating factor (GAF) (1,6,7). GAF is translocated to the nucleus (8), where it binds to gamma-activating sequences (GASs) in the promoters of target genes and activates transcription through the transactivator domain of STAT1 (1).…”
Section: Introductionmentioning
confidence: 99%