Expression of protein kinase C isoforms in renal tissue

Östlund, Eva; Méndez, Carlos F.; Jacobsson, Gunilla; Fryckstedt, Jessica; Meister, Björn; Aperia, Anita

doi:10.1038/ki.1995.117

Cited by 38 publications

(28 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Numerous studies document the growth-promoting properties of PKC; however, there is increasing evidence that some PKC isozymes are involved in cell growth inhibition and differentiation (reviewed in reference 13). In renal tissue, PKC ␣, ␦, and are the most abundant isozymes, while PKC ε is weakly but uniformly expressed in both the cortex and the medulla during ontogeny (40). Previous studies have shown that activated PKC ε inhibits cell growth in some tissues (32,46).…”

Section: Discussionmentioning

confidence: 99%

Cellular Activation Triggered by the Autosomal Dominant Polycystic Kidney Disease Gene Product PKD2

Arnould

Sellin

Benzing

et al. 1999

Molecular and Cellular Biology

View full text Add to dashboard Cite

Autosomal dominant polycystic kidney disease (ADPKD) is caused by germ line mutations in at least three ADPKD genes. Two recently isolated ADPKD genes, PKD1 and PKD2, encode integral membrane proteins of unknown function. We found that PKD2 upregulated AP-1-dependent transcription in human embryonic kidney 293T cells. The PKD2-mediated AP-1 activity was dependent upon activation of the mitogen-activated protein kinases p38 and JNK1 and protein kinase C (PKC) , a calcium-independent PKC isozyme. Staurosporine, but not the calcium chelator BAPTA [1,2-bis(o-aminophenoxy)ethane-N,N,N,N-tetraacetate], inhibited PKD2-mediated signaling, consistent with the involvement of a calcium-independent PKC isozyme. Coexpression of PKD2 with the interacting C terminus of PKD1 dramatically augmented PKD2-mediated AP-1 activation. The synergistic signaling between PKD1 and PKD2 involved the activation of two distinct PKC isozymes, PKC ␣ and PKC , respectively. Our findings are consistent with others that support a functional connection between PKD1 and PKD2 involving multiple signaling pathways that converge to induce AP-1 activity, a transcription factor that regulates different cellular programs such as proliferation, differentiation, and apoptosis. Activation of these signaling cascades may promote the full maturation of developing tubular epithelial cells, while inactivation of these signaling cascades may impair terminal differentiation and facilitate the development of renal tubular cysts.Human autosomal dominant polycystic kidney disease (ADPKD), one of the most prevalent inherited disorders with an incidence of 1 in 500 to 1 in 1,000 individuals, is characterized by the development of gradually enlarging renal epithelial cysts that progressively impair renal function (16,17). The vast majority of patients are affected by mutations in one of three ADPKD genes (7,27,43). PKD1 is mutated in more than 85% of ADPKD patients, and it encodes a large integral glycoprotein with multiple transmembrane domains and a large extracellular domain with significant homology to membrane proteins involved in cell-cell and/or cell-matrix interactions (1,2,20,21,45). PKD2 encodes a 968-amino-acid integral membrane protein with six transmembrane domains, and it is mutated in approximately 10 to 15% of all patients (35). Despite homologies to the family of voltage-gated calcium channel ␣ 1 subunits, the function of PKD2 remains elusive.It has been hypothesized that PKD1 and PKD2 function in a common signaling pathway. Patients with PKD1 and those with PKD2 have a similar clinical phenotype, while both PKD1 Ϫ/Ϫ and PKD2 Ϫ/Ϫ mice develop kidney and liver cysts resembling the human phenotype (30, 54). Recent studies have shown that PKD1 and PKD2 interact via their C-terminal cytoplasmic domains (41, 52). Thus, PKD1 and PKD2 appear to work in conjunction with each other, but it remains unclear by which mechanism they control tubular proliferation and differentiation and thereby prevent cyst formation. Cystic epithelial cells are thought to be incomp...

show abstract

Section: Discussionmentioning

confidence: 99%

Cellular Activation Triggered by the Autosomal Dominant Polycystic Kidney Disease Gene Product PKD2

Arnould

Sellin

Benzing

et al. 1999

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

“…In this study, we demonstrate that the ANG II stimulation of CD renin occurs via a Ca 2ϩ -dependent PKC and that increases in intracellular Ca 2ϩ are not enough to enhance prorenin or renin expression. PKC-␣ is the most abundant isoform present in renal CD cells (33). We used a PKC-␣ dominant negative, which expresses mutated nonfunctional PKC-␣, competing with the normal isoforms to specifically suppress PKC-␣ activity.…”

Section: Discussionmentioning

confidence: 99%

PKC-α-dependent augmentation of cAMP and CREB phosphorylation mediates the angiotensin II stimulation of renin in the collecting duct

González

Liu

Lara

et al. 2015

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

In contrast to the negative feedback of angiotensin II (ANG II) on juxtaglomerular renin, ANG II stimulates renin in the principal cells of the collecting duct (CD) in rats and mice via ANG II type 1 (AT 1R) receptor, independently of blood pressure. In vitro data indicate that CD renin is augmented by AT 1R activation through protein kinase C (PKC), but the exact mechanisms are unknown. We hypothesize that ANG II stimulates CD renin synthesis through AT 1R via PKC and the subsequent activation of cAMP/PKA/CREB pathway. In M-1 cells, ANG II increased cAMP, renin mRNA (3.5-fold), prorenin, and renin proteins, as well as renin activity in culture media (2-fold). These effects were prevented by PKC inhibition with calphostin C, PKC-␣ dominant negative, and by PKA inhibition. Forskolin-induced increases in cAMP and renin expression were prevented by calphostin C. PKC inhibition and Ca 2ϩ depletion impaired ANG II-mediated CREB phosphorylation and upregulation of renin. Adenylate cyclase 6 (AC) siRNA remarkably attenuated the ANG II-dependent upregulation of renin mRNA. Physiological activation of AC with vasopressin increased renin expression in M-1 cells. The results suggest that the ANG II-dependent upregulation of renin in the CD depends on PKC-␣, which allows the augmentation of cAMP production and activation of PKA/CREB pathway via AC6. This study defines the intracellular signaling pathway involved in the ANG II-mediated stimulation of renin in the CD. This is a novel mechanism responsible for the regulation of local renin-angiotensin system in the distal nephron.prorenin; hypertension; protein kinase; calcium; adenylyl cyclase-6; gene expression; M-1 cells IN ANGIOTENSIN II -(ANG II) dependent hypertension, the intrarenal ANG II content is greater than can be explained from the levels found in plasma (30, 31). High intrarenal ANG II levels can be partially explained by enhanced ANG II type 1 receptor (AT 1 R)-mediated uptake of ANG II (10). Augmentation of proximal tubule angiotensinogen (AGT) synthesis and secretion is responsible for increased local intratubular ANG II generation (21). The presence of AGT in the urine indicates that AGT traverses the distal nephron segments where it may then be cleaved to ANG I, if an adequate source of renin is available.In addition to the juxtaglomerular cells (JG), renin expression has been described in the proximal tubules, connecting tubules, and cortical and medullary collecting duct (CD) cells from the mouse, rat, and human kidney (39, 44). In contrast to JG cells, in the principal cells of the CD renin is upregulated by ANG II (36), via an AT 1 R-mediated mechanism (37), which is independent of blood pressure (35). In ANG II-dependent hypertensive rats with marked plasma renin activity (PRA) suppression, increased urinary levels of renin and prorenin reflect their augmented secretion by CD cells into the luminal fluid (26). In this model of experimental hypertension, intraluminal conversion of ANG I to ANG II in the CD is supported by the local presence of angiotens...

show abstract

“…All isoforms express distinct enzymological properties, differential tissue distribution, different substrate specificity, and specific subcellular localization with distinct modes of cellular regulation (4,6,9,18,23,36,38). For example, PKC␣, ␦, ⑀, and , but not PKC␤, which is strongly expressed in cardiomycytes, were detected in rat MC as determined by Western blotting (18,19,42).…”

mentioning

confidence: 99%

Protein kinase Cα participates in activation of store-operated Ca²⁺ channels in human glomerular mesangial cells

Kudlacek

Sansom

2002

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

(MC). The present study was performed to determine the specific isoform(s) of conventional PKC involved in activating SOC in MC. Fura 2 fluorescence ratiometry showed that the thapsigargin-induced Ca 2ϩ entry (equivalent to SOC) was significantly inhibited by 1 M Gö -6976 (a specific PKC␣ and ␤I inhibitor) and PKC␣ antisense treatment (2.5 nM for 24-48 h). However, LY-379196 (PKC␤ inhibitor) and 2,2Ј,3,3Ј,4,4Ј-hexahydroxy-1,1Ј-biphenyl-6,6Ј-dimethanoldimethyl ether (HBDDE; PKC␣ and ␥ inhibitor) failed to affect thapsigargin-evoked activation of SOC. Single-channel analysis in the cell-attached configuration revealed that Gö -6976 and PKC␣ antisense significantly depressed thapsigargin-induced activation of SOC. However, LY-379196 and HBDDE did not affect the SOC responses. In inside-out patches, application of purified PKC␣ or ␤I, but not ␤II or ␥, significantly rescued SOC from postexcision rundown. Western blot analysis revealed that thapsigargin evoked a decrease in cytosolic expression with a corresponding increase in membrane expression of PKC␣ and ␥. However, the translocation from cytosol to membranes was not detected for PKC␤I or ␤II. These results suggest that PKC␣ participates in the intracellular signaling pathway for activating SOC upon release of intracellular stores of Ca 2ϩ

show abstract

Expression of protein kinase C isoforms in renal tissue

Cited by 38 publications

References 20 publications

Cellular Activation Triggered by the Autosomal Dominant Polycystic Kidney Disease Gene Product PKD2

Cellular Activation Triggered by the Autosomal Dominant Polycystic Kidney Disease Gene Product PKD2

PKC-α-dependent augmentation of cAMP and CREB phosphorylation mediates the angiotensin II stimulation of renin in the collecting duct

Protein kinase Cα participates in activation of store-operated Ca²⁺ channels in human glomerular mesangial cells

Contact Info

Product

Resources

About

Expression of protein kinase C isoforms in renal tissue

Cited by 38 publications

References 20 publications

Cellular Activation Triggered by the Autosomal Dominant Polycystic Kidney Disease Gene Product PKD2

Cellular Activation Triggered by the Autosomal Dominant Polycystic Kidney Disease Gene Product PKD2

PKC-α-dependent augmentation of cAMP and CREB phosphorylation mediates the angiotensin II stimulation of renin in the collecting duct

Protein kinase Cα participates in activation of store-operated Ca2+ channels in human glomerular mesangial cells

Contact Info

Product

Resources

About

Protein kinase Cα participates in activation of store-operated Ca²⁺ channels in human glomerular mesangial cells