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An international collaboration of the Potter Group with Solomon Snyder’s Group in the USA and with Chinese and German colleagues has uncovered the myo-inositol polyphosphate pyrophosphate 5-InsP7 as a regulator of the Na⁺/K⁺- ATPase-α1

Inositol hexakisphosphate kinase 1 associates with PI 3-kinase PI3K p85α and generates a local pool of 5-InsP7, which binds the RhoGAP domain of PI3K p85α. 5-InsP7 Binding disinhibits the PI3K p85α interaction with Na⁺/K⁺-ATPase-α1, recruiting AP2 that mediates clathrin-mediated endocytosis leading to downstream degradation of Na⁺/K⁺-ATPase-α1. The structure of 5-InsP7 is illustrated.
Model for 5-InsP7 regulation of Na⁺/K⁺-ATPase-α1 endocytosis and downstream degradation. Inositol hexakisphosphate kinase 1 associates with PI 3-kinase PI3K p85α and generates a local pool of 5-InsP7, which binds the RhoGAP domain of PI3K p85α. 5-InsP7 Binding disinhibits the PI3K p85α interaction with Na⁺/K⁺-ATPase-α1, recruiting AP2 that mediates clathrin-mediated endocytosis leading to downstream degradation of Na⁺/K⁺-ATPase-α1. The structure of 5-InsP7 is illustrated.

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