Class II/III PI3Ks ( @entity7425 3-kinases) produce the @entity8736 lipid that is involved in intracellular vesicular trafficking. In contrast with class I PI3Ks, the potential signalling roles of class II/III PI3Ks are poorly understood. In a recent article in the Biochemical Journal, Bago and co-workers report that @entity26814 ( @entity26814 ), the only class III @entity10412 , controls the activity of @entity68333 ( @entity68333 ). Like other AGC kinases, the SGKs ( @entity15188 , @entity68334 and @entity68333 ) are activated by dual phosphorylation. Unlike its cousins @entity15188 and @entity68334 , @entity68333 contains a PtdIns(3)P-binding domain, providing an additional element of regulation. The study by Bago et al. characterizes and makes extensive use of a Novartis @entity26814 inhibitor ( @entity26814 -IN1) that inhibits this @entity10412 isoform with nanomolar potency, without affecting other lipid kinases or more than 300 protein kinases. The authors show that this compound very rapidly reduced @entity8736 levels at the endosome with concomitant loss of @entity68333 phosphorylation. Co-inhibition of class I PI3Ks led to a further reduction in @entity68333 activity, indicating that class I PI3Ks may also regulate @entity68333 activity through an additional, currently unknown, mechanism. It remains to be assessed whether the novel @entity10412 -protein kinase connection established by this study is subject to acute cellular stimulation or is part of a constitutive housekeeping function. @entity26814 -IN1 will provide a useful tool to decipher the kinase-dependent functions of @entity26814 , with acute changes in @entity68333 phosphorylation and subcellular localization being new biomarkers of @entity26814 activity.

Cinderella finds her shoe: the first XXXX inhibitor uncovers a new @entity10412 -AGC protein kinase connection.

@entity8736 :: ('MESH:C055525', 'Chemical') :: ['PtdIns(3)P'] @entity7425 :: ('CHEBI:18179', 'Chemical') :: ['phosphoinositide'] @entity68334 :: ('10110', 'Gene') :: ['SGK2'] @entity15188 :: ('6446', 'Gene') :: ['SGK1'] @entity10412 :: ('5293', 'Gene') :: ['PI3K'] @entity68333 :: ('23678', 'Gene') :: ['SGK3', 'serum- and glucocorticoid-regulated protein kinase 3'] @entity26814 :: ('5289', 'Gene') :: ['vacuolar protein sorting 34', 'VPS34', 'Vps34']
@entity26814 :: (5289,Gene) :: ['Vps34']
