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Cho KJ, Park JH, Hancock JF. Staurosporine: A new tool for studying phosphatidylserine trafficking. Commun Integr Biol. 2013;6(4):e24746doi: 10.4161/cib.24746.
Cho, K. J., Park, J. H., & Hancock, J. F. (2013). Staurosporine: A new tool for studying phosphatidylserine trafficking. Communicative & integrative biology, 6(4), e24746. https://doi.org/10.4161/cib.24746
Cho, Kwang-Jin, et al. "Staurosporine: A new tool for studying phosphatidylserine trafficking." Communicative & integrative biology vol. 6,4 (2013): e24746. doi: https://doi.org/10.4161/cib.24746
Cho KJ, Park JH, Hancock JF. Staurosporine: A new tool for studying phosphatidylserine trafficking. Commun Integr Biol. 2013 Jul 01;6(4):e24746. doi: 10.4161/cib.24746. Epub 2013 May 10. PMID: 23986809; PMCID: PMC3737755.
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Commun Integr Biol. 2013 Jul 01;6(4):e24746. doi: 10.4161/cib.24746. Epub 2013 May 10.

Staurosporine: A new tool for studying phosphatidylserine trafficking.

Communicative & integrative biology

Kwang-Jin Cho, Jin-Hee Park, John F Hancock

Affiliations

  1. Department of Integrative Biology and Pharmacology; The University of Texas Medical School at Houston; Houston, TX USA.

PMID: 23986809 PMCID: PMC3737755 DOI: 10.4161/cib.24746

Abstract

The Ras GTPases comprising three main isoforms H-, N- and K-Ras operate at the plasma membrane as molecular switches in essential signaling pathways. Active concentration of the minor phospholipid phosphatidylserine in the inner leaflet of the plasma membrane contributes to the electrostatic potential that is required for K-Ras anchoring to the plasma membrane. We recently observed that staurosporine and related analogs: 7-oxostaurosporine, UCN-01 and UCN-02, long known as relatively non-specific protein kinase inhibitors, block endosomal sorting and recycling of phosphatidylserine, resulting in redistribution of phosphatidylserine to endosomes and endomembranes with concomitant mislocalization of K-Ras. Staurosporines are therefore a new tool to study phosphatidylserine trafficking. We discuss whether the mechanism of action of UCN-01, an FDA-approved staurosporine analog used as an anti-cancer therapeutic, is related to effects on phosphatidylserine subcellular distribution. Given the high prevalence of expression of constitutively active K-Ras in human cancers, we ask whether inhibitors of phosphatidylserine trafficking may have important therapeutic applications.

Keywords: Ras GTPase; UCN-01; lipid recycling; phosphatidylserine; staurosporine

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