Reactome | STAT3,STAT6 bind p-Y-IL4R

STAT3,STAT6 bind p-Y-IL4R

Stable Identifier

R-HSA-6786124

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol, extracellular region, plasma membrane

ReviewStatus

5/5

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Signal transducer and activator of transcription 6 (STAT6) binds to tyrosine-phosphorylated Interleukin-4 receptor subunit alpha (IL4R) (Hou et al. 1994, Schindler et al. 1996, Mikita et al. 1998). Binding of STAT3 has also been reported (Rahaman et al. 2005, Bhattacharjee et al. 2013) but is sometimes reported to be dependent on interleukin-13 receptor subunit alpha (IL13RA) rather than IL4R (Umeshita-Suyama et al. 2000). Other reports have suggested that STAT3 is not phosphorylated in response to IL4 (Friedrich et al. 1999). Consistent with the fact that IL4 and IL13 receptors both incorporate IL4R, they also share common signaling pathways. IL4R is believed to be the signaling component of both IL4 and IL13 receptors because treatment with either generates intermediates that are characteristic of IL4 responses, including phosphorylation of IL4R, insulin receptor substrate 2 (IRS2), Janus kinase 1 (JAK1), and Non-receptor tyrosine-protein kinase 2 (TYK2) (Welham et al. 1995). STAT6-deficient mice suggest that IL13 signaling, like IL4 signaling, uses STAT6 (Takeda et al. 1996, Kaplan et al. 1996). STAT1 activation in response to IL4 has been reported (Wang et al. 2004) but also disputed (Bhattacharjee et al. 2013).

Literature References

PubMed ID	Title	Journal	Year
15805299	Aberrant Stat3 signaling by interleukin-4 in malignant glioma cells: involvement of IL-13Ralpha2 Rahaman, SO, Haque, SJ, Vogelbaum, MA	Cancer Res.	2005
8085155	An interleukin-4-induced transcription factor: IL-4 Stat Henzel, WJ, Schindler, U, Ho, TC, Hou, J, Brasseur, M, McKnight, SL	Science	1994
23124025	IL-4 and IL-13 employ discrete signaling pathways for target gene expression in alternatively activated monocytes/macrophages Yakubenko, VP, Mulya, A, Cathcart, MK, Kundu, S, Bhattacharjee, A, Shukla, M	Free Radic. Biol. Med.	2013
9651359	Mutational analysis of the STAT6 SH2 domain Schindler, U, Mikita, T, Daniel, C, Wu, P	J. Biol. Chem.	1998
7796300	Components of a Stat recognition code: evidence for two layers of molecular selectivity Schindler, U, Rothe, M, Brasseur, M, McKnight, SL, Wu, P	Immunity	1995