Limited Proteolysis of Protein Kinase C Subspecies by Calcium-dependent Neutral Protease (Calpain)

Kishimoto, Akira; Mikawa, Katsuya; Hashimoto, Kenji; Yasuda, Ichiro; Tanaka, Shinichiro; Tominaga, Masahiro; Kuroda, Tomoya; Nishizuka, Yasutomi

doi:10.1016/s0021-9258(19)84966-9

Cited by 433 publications

(26 citation statements)

References 15 publications

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“…Two constructs were generated with differing lengths of the hinge to test whether the hinge served a stabilizing role similar to that of the A helix in protein kinase A [20]: Cat285 and Cat307, which include 55 and 33 residues respectively, preceding the kinase [18] (Figure 1). The shorter protein corresponds to the proteolytically-generated kinase core: trypsin cleaves at K307 and K309 [21] and calpain at G309 and K318 [22].…”

Section: Characterization Of Kinase-domain Constructs Of Protein Kinase C β βIimentioning

confidence: 99%

The hydrophobic phosphorylation motif of conventional protein kinase C is regulated by autophosphorylation

1999

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PKC betaII autophosphorylates at its conserved carboxy-terminal hydrophobic phosphorylation site by an apparently intramolecular mechanism. Expression studies with kinase-inactive mutants revealed that this mechanism is the only one responsible for phosphorylating this motif in vivo. Thus, conventional PKC autoregulates the carboxy-terminal phosphorylation switch following phosphorylation by another kinase at the activation loop switch.

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Section: Characterization Of Kinase-domain Constructs Of Protein Kinase C β βIimentioning

confidence: 99%

The hydrophobic phosphorylation motif of conventional protein kinase C is regulated by autophosphorylation

1999

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“…We found that since the cortisol response to OAG plus A23187 was attenuated by prior exposure to PAF (Fig. 6B) or this mixture (Shimada et al 2005; Table 1), the membrane-associated form of PKC might be readily degraded by proteolysis (Kishimoto et al 1989).…”

Section: Discussionmentioning

confidence: 90%

Cross-regulation of cortisol secretion by adrenocorticotropin and platelet-activating factor in perfused guinea pig adrenals

Shimada

Hirose

Matsumoto

et al. 2007

Journal of Endocrinology

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We examined the cross-regulation of signaling between ACTH-and platelet-activating factor (PAF)-mediated steroidogenesis in the perfused guinea pig adrenal gland. Our method of in situ perfusion using an artificial medium can evaluate whether cortisol secretion in response to ACTH and PAF is interactive. Treating adrenal glands with 100 pg/ml ACTH diminished the subsequent cortisol response to 10 nM PAF. By contrast, PAF resulted in subsequent potentiation of ACTH-induced cortisol secretion. A mixture of 50 microM L-alpha-1-oleoyl-2-acetyl-sn-glycerol (OAG), an activator of protein kinase C (PKC), and 3.3 microM calcium ionophore (A23187), or 10 microM forskolin (FRK) diminished the cortisol response to PAF, whereas that to ACTH was unaffected. Each of PAF, ACTH, or FRK eliminated the cortisol response to OAG plus A23187, whereas that to FRK was unaffected. These data show that the protein kinase A (PKA)-dependent processes activated by ACTH or FRK can interfere with PAF-induced signal transduction at receptor and post-receptor levels. In contrast, PKC-dependent processes activated by PAF promoted ACTH-signaling at receptor and post-receptor level. Cross-regulation between processes activated by PAF receptor-PKC and by ACTH receptor-PKA might function in the multifactorial regulation of adrenocortical steroidogenesis.

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“…Calpain-2 from porcine kidney does not directly bind phospholipid phosphates in vitro. Calpain-2 was reported to associate with various phospholipids (7) and play a role in cleaving protein kinase C (27). To determine whether calpain-2 directly binds phospholipid phosphates and, if it binds to lipids, to which lipids, we performed PIP strip overlay binding assays (described in MATERIALS AND METHODS).…”

Section: Resultsmentioning

confidence: 99%

“…We previously showed that PKC activity reduces the association between ENaC and MARCKS, presumably from MARCKS translocating to the cytoplasm after serine residues within the effector domain are phosphorylated (3). PKC was shown to be a substrate of calpain (27,33,39). The degradation of PKC␣ by calpain would increase the amount of MARCKS at the membrane provided that other Ca 2ϩ -dependent mechanisms such as Ca 2ϩ -calmodulin binding to MARCKS or activation of CaMKII do not compensate for the loss of PKC␣ activity.…”

Section: C49mentioning

confidence: 99%

ENaC activity is regulated by calpain-2 proteolysis of MARCKS proteins

Montgomery

Ghazi

et al. 2017

American Journal of Physiology-Cell Physiology

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We previously demonstrated a role for the myristoylated alanine-rich C kinase substrate (MARCKS) to serve as an adaptor protein in the anionic phospholipid phosphate-dependent regulation of the epithelial sodium channel (ENaC). Both MARCKS and ENaC are regulated by proteolysis. Calpains are a family of ubiquitously expressed intracellular Ca-dependent cysteine proteases involved in signal transduction. Here we examine the role of calpain-2 in regulating MARCKS and ENaC in cultured renal epithelial cells and in the mouse kidney. Using recombinant fusion proteins, we show that MARCKS, but not the ENaC subunits, are a substrate of calpain-2 in the presence of Ca Pharmacological inhibition of calpain-2 alters MARCKS protein expression in light-density sucrose gradient fractions from cell lysates of mouse cortical collecting duct cells. Calpain-dependent cleaved products of MARCKS are detectable in cultured renal cells. Ca mobilization and calpain-2 inhibition decrease the association between ENaC and MARCKS. The inhibition of calpain-2 reduces ENaC activity as demonstrated by single-channel patch-clamp recordings and transepithelial current measurements. These results suggest that calpain-2 proteolysis of MARCKS promotes its interaction with lipids and ENaC at the plasma membrane to allow for the phosphatidylinositol 4,5-bisphosphate (PIP2)-dependent regulation of ENaC activity in the kidney.

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Limited Proteolysis of Protein Kinase C Subspecies by Calcium-dependent Neutral Protease (Calpain)

Cited by 433 publications

References 15 publications

The hydrophobic phosphorylation motif of conventional protein kinase C is regulated by autophosphorylation

The hydrophobic phosphorylation motif of conventional protein kinase C is regulated by autophosphorylation

Cross-regulation of cortisol secretion by adrenocorticotropin and platelet-activating factor in perfused guinea pig adrenals

ENaC activity is regulated by calpain-2 proteolysis of MARCKS proteins

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