Extended Data Fig. 2: Activation of IP6K1 by PKC/D-mediated phosphorylation and consequent conformational changes. | Nature Metabolism

Extended Data Fig. 2: Activation of IP6K1 by PKC/D-mediated phosphorylation and consequent conformational changes.

From: 5-IP7 is a GPCR messenger mediating neural control of synaptotagmin-dependent insulin exocytosis and glucose homeostasis

Extended Data Fig. 2: Activation of IP6K1 by PKC/D-mediated phosphorylation and consequent conformational changes.

(a) The catalytic activity of IP6K1 with or without phosphorylation by PKC or PKD, assayed by the PAGE gel method, suggest that single kinase phosphorylation only modestly improves IP6K1 enzymatic activity. (b) The catalytic activities of the S118D/S121D (DD) phospho-mimic mutant is higher than wildtype IP6K1. (c) The catalytic activity of IP6K1 wildtype, S118D and S121D single mutants are comparable. (d) Limited tryptic proteolysis of unmodified or phosphorylated IP6K1 reveal slowed digest upon phosphorylation. (e) Circular dichroism analysis of WT (upper panel) or DD mutant (lower panel) IP6K1 with or without urea at the indicated concentrations. 3-4 M urea totally denatures WT but not DD mutant IP6K1. (f) Scheme depicting the proposed mechanism of IP6K1 activation by PKC phosphorylation.

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