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Staurosporine: A New Tool for Studying Phosphatidylserine Trafficking

Staurosporine: A New Tool for Studying Phosphatidylserine Trafficking

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

Commun Integr Biol. 2013 Jul 1;6(4):e24746.

PMID: 23986809

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP125035838	7-Oxostaurosporine		125035-83-8	Price

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