Reactome | Heparin binds PKR

Heparin binds PKR

Stable Identifier

R-HSA-9835121

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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Heparin is a mixture of glycosaminoglycan polymers of different sizes and is commercially available as mixtures of predominantly hexamers, octamers, or hexadecamers (Hep-6, Hep-8, Hep-16). PKR (EIF2AK2) binds Hep-8 and Hep-16, but not Hep-6, leading to its dimerization and autophosphorylaton. This activation has also been shown to occur following treatment of vascular smooth muscle cells with heparin, resulting in antiproliferative effects through PKR-mediated signaling. These results indicate that PKR can be activated by small molecules and is a viable target for the development of novel antiviral agents (George et al, 1996; Patel et al, 2002; Fasciano et al, 2005; Anderson et al, 2011).

Literature References

PubMed ID	Title	Journal	Year
21978664	Heparin activates PKR by inducing dimerization Lary, JW, Anderson, E, Cole, JL, Pierre-Louis, WS, Wong, CJ	J Mol Biol	2011
12231563	Contribution of double-stranded RNA-activated protein kinase toward antiproliferative actions of heparin on vascular smooth muscle cells Handy, I, Patel, CV, Patel, RC	Arterioscler Thromb Vasc Biol	2002
8661426	Characterization of the heparin-mediated activation of PKR, the interferon-inducible RNA-dependent protein kinase McCormack, SJ, Svahn, CM, George, CX, Samuel, CE, Thomis, DC	Virology	1996
15752359	Identification of the heparin-binding domains of the interferon-induced protein kinase, PKR Handy, I, Fasciano, S, Hutchins, B, Patel, RC	FEBS J	2005