STAT3

GeneName

STAT3

Summary

STAT3, also known as STAT-3 or APRF, is an 88 kDa transcription factor that plays a pivotal role in various cellular processes. It is expressed in multiple tissues, including the brain, liver, and immune cells, and is localised in the nucleus, cytoplasm, and at the plasma membrane. STAT3 is activated by cytokines and growth factors through the JAK-STAT signalling pathway, leading to its dimerization and translocation to the nucleus where it regulates gene expression. It binds to specific DNA sequences to modulate transcription of target genes involved in cell differentiation, proliferation, and survival, particularly in response to interleukins and hormones. Additionally, it participates in the regulation of immune responses and inflammatory processes, highlighting its importance in both normal physiology and disease states.

Importance

STAT3 is relevant to: - Cancer progression and metastasis due to its role in promoting cell survival and proliferation - Inflammatory diseases as it mediates responses to cytokines involved in inflammation - Neurodegenerative disorders through its involvement in neuronal survival and differentiation - Metabolic regulation, particularly in response to leptin and other hormones affecting energy homeostasis - Autoimmune conditions, where it influences T-helper cell differentiation and immune responses

Top Products

For researchers investigating STAT3, we highly recommend the top-selling recombinant antibody, Anti-STAT3 antibody [EPR787Y] (ab68153). This well-cited antibody has garnered 546 citations, reflecting its strong reputation in the field. It has been validated in knockout models and is suitable for a variety of applications, including Western blotting (WB), immunohistochemistry (IHC), immunocytochemistry (ICC), and flow cytometry (FC). This versatility makes it an excellent choice for those seeking reliable and consistent results in their STAT3 studies. The Anti-STAT3 antibody ELISA Kit (ab226942), supported by 5 citations, is an excellent option for researchers looking to accurately measure STAT3 levels in their samples.

Abcam Product Citation Summary

The data indicates a significant focus on the role of STAT3 in various human and mouse cell types, particularly in cancer research, immune response, and cellular signaling pathways. The use of Abcam antibodies in studies involving human colon cancer, osteosarcoma, and lung tissues highlights the importance of STAT3 in tumour biology and treatment responses. Additionally, the involvement of STAT3 in G-CSF-mediated signaling and the effects of leptin suggests its broader implications in physiological processes.

Abcam Product Citation Table

Function

Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors (PubMed:10688651, PubMed:12359225, PubMed:12873986, PubMed:15194700, PubMed:15653507, PubMed:16285960, PubMed:17344214, PubMed:18242580, PubMed:18782771, PubMed:22306293, PubMed:23084476, PubMed:28262505, PubMed:32929201, PubMed:38404237). Once activated, recruits coactivators, such as NCOA1 or MED1, to the promoter region of the target gene (PubMed:15653507, PubMed:16285960, PubMed:17344214, PubMed:18782771, PubMed:28262505, PubMed:32929201). May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4 (PubMed:12873986). 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 (PubMed:12359225). Activated by IL31 through IL31RA (PubMed:15194700). Acts as a regulator of inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg): acetylation promotes its transcription activity and cell differentiation while deacetylation and oxidation of lysine residues by LOXL3 inhibits differentiation (PubMed:28065600, PubMed:28262505). Involved in cell cycle regulation by inducing the expression of key genes for the progression from G1 to S phase, such as CCND1 (PubMed:17344214). Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation (By similarity). May play an apoptotic role by transctivating BIRC5 expression under LEP activation (PubMed:18242580). Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity (PubMed:23084476). Plays a crucial role in basal beta cell functions, such as regulation of insulin secretion (By similarity). Following JAK/STAT signaling activation and as part of a complex with NFATC3 and NFATC4, binds to the alpha-beta E4 promoter region of CRYAB and activates transcription in cardiomyocytes (By similarity).

Involvement in disease

Hyper-IgE syndrome 1, autosomal dominant, with recurrent infections

HIES1

A rare disorder of immunity and connective tissue characterized by immunodeficiency, chronic eosinophilia, distinctive coarse facial appearance, abnormal dentition, hyperextensibility of the joints, and bone fractures.

None

The disease is caused by variants affecting the gene represented in this entry.

Autoimmune disease, multisystem, infantile-onset, 1

ADMIO1

A disorder characterized by early childhood onset of a spectrum of autoimmune manifestations affecting multiple organs, including insulin-dependent diabetes mellitus and autoimmune enteropathy or celiac disease. Other features include short stature, non-specific dermatitis, hypothyroidism, autoimmune arthritis, and delayed puberty.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Tyrosine phosphorylated upon stimulation with EGF. Tyrosine phosphorylated in response to constitutively activated FGFR1, FGFR2, FGFR3 and FGFR4 (By similarity). Activated through tyrosine phosphorylation by BMX. Tyrosine phosphorylated in response to IL6, IL11, LIF, CNTF, KITLG/SCF, CSF1, EGF, PDGF, IFN-alpha, LEP and OSM. Activated KIT promotes phosphorylation on tyrosine residues and subsequent translocation to the nucleus. Phosphorylated on serine upon DNA damage, probably by ATM or ATR. Serine phosphorylation is important for the formation of stable DNA-binding STAT3 homodimers and maximal transcriptional activity. ARL2BP may participate in keeping the phosphorylated state of STAT3 within the nucleus. Upon LPS challenge, phosphorylated within the nucleus by IRAK1. Upon erythropoietin treatment, phosphorylated on Ser-727 by RPS6KA5. Dephosphorylation on tyrosine residues by PTPN2 negatively regulates IL6/interleukin-6 signaling (By similarity). Phosphorylation at Tyr-705 by PTK6, isoform M2 of PKM (PKM2) or FER leads to an increase of its transcriptional activity (PubMed:12763138, PubMed:16568091, PubMed:21135090, PubMed:22306293, PubMed:32929201). Phosphorylation at Tyr-705 is increased in the presence of calcineurin (By similarity). Phosphorylation at Tyr-640 by TYK2 negatively regulates transcriptional activity (PubMed:29162862).

Acetylated on lysine residues by EP300/p300, promoting its activation (PubMed:15653507, PubMed:16285960, PubMed:18782771). Acetylation at Lys-49 and Lys-87 by EP300/p300 promotes its activation (PubMed:15653507, PubMed:16285960, PubMed:28262505). Acetylation at Lys-87 by EP300/p300 promotes its association with BRD2 and recruitment to chromatin (PubMed:28262505). Deacetylated at Lys-49 and Lys-87 by HDAC1 (PubMed:16285960). Acetylation at Lys-685 by EP300/p300 promotes its homodimerization and activation (PubMed:15653507). Deacetylated at Lys-685 by HDAC3 (PubMed:15653507). Acetylated on lysine residues by CREBBP (PubMed:28065600). Deacetylation by LOXL3 leads to disrupt STAT3 dimerization and inhibit STAT3 transcription activity (PubMed:28065600). Oxidation of lysine residues to allysine on STAT3 preferentially takes place on lysine residues that are acetylated (PubMed:28065600).

Some lysine residues are oxidized to allysine by LOXL3, leading to disrupt STAT3 dimerization and inhibit STAT3 transcription activity (PubMed:28065600). Oxidation of lysine residues to allysine on STAT3 preferentially takes place on lysine residues that are acetylated (PubMed:28065600).

(Microbial infection) Phosphorylated on Tyr-705 in the presence of S.typhimurium SarA.

Methylated at Lys-140. Demethylation at Lys-140 by Jmjd1c facilitates its dephosphorylation by Ptpn6.

Sequence Similarities

Belongs to the transcription factor STAT family.

Tissue Specificity

Heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Expressed in naive CD4(+) T cells as well as T-helper Th17, Th1 and Th2 cells (PubMed:31899195).

Cellular localization

• Cytoplasm
• Nucleus
• Shuttles between the nucleus and the cytoplasm (PubMed:29162862). Translocated into the nucleus upon tyrosine phosphorylation and dimerization, in response to signaling by activated FGFR1, FGFR2, FGFR3 or FGFR4 (PubMed:15653507, PubMed:16285960). Constitutive nuclear presence is independent of tyrosine phosphorylation. Predominantly present in the cytoplasm without stimuli. Upon leukemia inhibitory factor (LIF) stimulation, accumulates in the nucleus. The complex composed of BART and ARL2 plays an important role in the nuclear translocation and retention of STAT3. Identified in a complex with LYN and PAG1. Translocates to the nucleus in the presence of EDN1 (By similarity).

Alternative names

APRF, STAT3, Signal transducer and activator of transcription 3, Acute-phase response factor

Database links

swissprot:P40763 omim:102582 entrezGene:6774

Other research areas

• Immuno-oncology
• Immunology & Infectious Disease
• Oncology