Regulatory domain determinants that control PKD1 activity.

The Journal of Biological Chemistry
Vitalyi O RybinSusan F Steinberg

Abstract

The canonical pathway for protein kinase D1 (PKD1) activation by growth factor receptors involves diacylglycerol binding to the C1 domain and protein kinase C-dependent phosphorylation at the activation loop. PKD1 then autophosphorylates at Ser(916), a modification frequently used as a surrogate marker of PKD1 activity. PKD1 also is cleaved by caspase-3 at a site in the C1-PH interdomain during apoptosis; the functional consequences of this cleavage event remain uncertain. This study shows that PKD1-Δ1-321 (an N-terminal deletion mutant lacking the C1 domain and flanking sequence that models the catalytic fragment that accumulates during apoptosis) and PKD1-CD (the isolated catalytic domain) display high basal Ser(916) autocatalytic activity and robust activity toward CREBtide (a peptide substrate) but little to no activation loop autophosphorylation and no associated activity toward protein substrates, such as cAMP-response element binding protein and cardiac troponin I. In contrast, PKD1-ΔPH (a PH domain deletion mutant) is recovered as a constitutively active enzyme, with high basal autocatalytic activity and high basal activity toward peptide and protein substrates. These results indicate that individual regions in the regu...Continue Reading

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Dec 16, 2010·The Journal of Biological Chemistry·Jianfen GuoSusan F Steinberg

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Citations

Mar 19, 2016·Journal of Cellular Physiology·Zhuo LiCheng Du
Aug 14, 2019·The Journal of Biological Chemistry·Daniel J ElsnerThomas A Leonard
Jun 2, 2018·Oxidative Medicine and Cellular Longevity·Mathias Cobbaut, Johan Van Lint
Jul 18, 2019·Molecular Cancer Research : MCR·Ilige Youssef, Jean-Marc Ricort
Sep 18, 2021·Molecular Pharmacology·Susan F Steinberg

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