Stat3 (rat, UniProt P52631): manual literature synthesis
Manual
Stat3 (rat, UniProt P52631): manual literature synthesis
No deep-research provider was run for this gene (no API keys in this session). This file
is a manual synthesis written from the cached publications in publications/ and the
UniProt record (Stat3-uniprot.txt). Every claim carries inline provenance.
Identity and family
- Rat Stat3 (P52631; RGD:3772; GeneID 25125) is a 770-aa member of the STAT transcription
factor family, with N-terminal, coiled-coil, DNA-binding (p53-like fold), linker, SH2 and
transactivation domains (InterPro IPR001217 STAT; IPR035855 STAT3_SH2)
[file:rat/Stat3/Stat3-uniprot.txt "Belongs to the transcription factor STAT family."].
- Rat Stat3 was first purified from acute-phase rat liver nuclei by DNA-affinity
chromatography on the IL-6 response element of the alpha2-macroglobulin gene
PMID:8530402.
Core molecular mechanism (cytokine-activated, sequence-specific transcription activator)
- Canonical activation: receptor-associated JAKs phosphorylate STATs on a tyrosine, STATs
dimerise and translocate to the nucleus to bind promoter elements
PMID:19450559.
- UniProt function summary [file:rat/Stat3/Stat3-uniprot.txt "Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors."]
and IL-6/gp130 acute-phase target genes [file:rat/Stat3/Stat3-uniprot.txt "Upon activation of IL6ST/gp130 signaling by interleukin-6 (IL6), binds to the IL6-responsive elements identified in the promoters of various acute-phase protein genes."].
- In rat cardiomyocytes, Stat3 forms a promoter-binding complex with NFAT and binds the
alphaBE4 element of the CryAB gene PMID:19538478.
- In rat hippocampal CA1, Stat3 occupies target promoters (survivin, Bcl-xL, Mn-SOD) after
ischemia and drives STAT3-dependent transcription PMID:23884942.
- Tyr705 is required: a Y705F dominant-negative Stat3 enhances cell death in rat neonatal
ventricular myocytes PMID:19450559.
Interactions recorded for the rat protein
Non-nuclear pools
- Mitochondria: STAT3 is imported into mitochondria in a GRIM-19-dependent manner and
resides in the inner membrane PMID:23271731.
- Pharmacological STAT3 inhibition (Stattic) in rat heart mitochondria increases ROS, lowers
ATP production and sensitises the permeability transition pore PMID:23590160.
Caveat: Stattic is a small-molecule inhibitor and these are pharmacological, not genetic, data.
- Postsynaptic density: Stat3 is found in the rat PSD PMID:10891587.
In rat hippocampal slices, STAT3 inhibition or knockdown blocks NMDAR-dependent LTD
PMID:22284190
by a non-nuclear, transcription-independent mechanism PMID:22284190.
Physiological contexts in rat (mostly perturbation / expression evidence)
- Acute-phase response in liver PMID:8530402.
- Cytoprotection of cardiomyocytes against ischemia/reperfusion PMID:19450559;
IL-6-activated Stat3 prevents cardiomyocyte apoptosis in haemorrhagic shock PMID:18270592.
- Estradiol neuroprotection after global ischemia via Stat3-dependent survivin
transcription PMID:23884942.
- IL-6-stimulated satellite-cell proliferation via JAK2/STAT3/cyclin D1 PMID:23869758;
ghrelin-stimulated hippocampal neural stem cell proliferation PMID:23608221.
- Prolactin-induced SERCA2 expression in islets PMID:17911393.
- TNF-induced IL-6 release from brain pericytes via NF-kB and JAK-STAT3 PMID:29702085.
- Hypoxia/SuHx pulmonary hypertension: phospho-STAT3 in CD4+ cells PMID:38602915.
Inferences
Rat Stat3 is ~99% identical to mouse and human STAT3, so the extensive mouse/human
literature (leptin signalling in hypothalamus, Th17 differentiation, gp130-family cytokine
signalling, autophagy repression via PKR, mitochondrial respiration) is transferred by ISO
annotations. These are plausible, but most of the organismal processes (feeding behaviour,
temperature homeostasis, glucose homeostasis) are downstream physiological consequences of
its transcriptional role in particular cell types rather than distinct activities.