Rab11 is phosphorylated by classical and novel protein kinase C isoenzymes upon sustained phorbol ester activation

Pavarotti, Martín; Capmany, Anahí; Vitale, Nicolas; Colombo, María Isabel; Damiani, Marı́a Teresa

doi:10.1111/boc.201100062

Cited by 25 publications

(20 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While blots using unpurified lysates from cells not induced with PMA revealed no visible band corresponding to phosphorylated Rabphilin 3A ( Figure 7A). This result suggests that PRKC proteins possibly target Rab effectors proteins, which is consistent with previous studies showing different Rab proteins as targets for PRKC isozymes [88,[90][91][92]. Further work will be necessary to characterize this possible functional link of phosphorylated Rabphilin 3a and exocytosis, however, the western blot is consistent with a role of PRKC in regulated exocytosis in MCF-7 cells.…”

Section: Pma-supporting

confidence: 89%

Imaging the rapid yet transient accumulation of regulatory lipids, lipid kinases, and protein kinases during membrane fusion, at sites of exocytosis of MMP-9 in cancer cells

Stephens

Powell

Taraska

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: The control of exocytosis is physiologically essential. In vitro SNARE proteins are sufficient to drive membrane fusion, but in cells there are additional proteins and lipids that work together to drive efficient, fast, and timely release of secretory vesicle cargo. Growing evidence suggests that regulatory lipids act as important lipid signals and regulate various biological processes including exocytosis. Though functional roles of many of these regulatory lipids has been linked to exocytosis, the dynamic behavior of these lipids during membrane fusion at sites of exocytosis in cell culture remains unknown. Methods: We used total internal reflection fluorescence microscopy (TIRF) to observe the spatial organization and temporal dynamics of several lipids, and accessory proteins, like lipid kinases and protein kinases, in the form of protein kinase C (PRKC) relative to single sites of exocytosis of MMP-9 in living MCF-7 cancer cells. Results: After stimulating exocytosis with PMA, we observed a transient accumulation of the regulatory lipids (e.g. PIP, PIP2, and DAG), lipid kinases (e.g. PI4K2B, PI4K3A, and PIP5KA), and protein kinases (e.g. PRKCA and PRKCE) at exocytic sites centered on the time of membrane fusion, before rapidly diffusing away from the fusion sites. Additionally, the synthesis of these regulatory lipids, degradation of these lipids, and the downstream effectors activated by these lipids, are also achieved by the recruitment and accumulation of key enzymes at exocytic sites (during the moment of cargo release), including lipid kinases, protein kinases, and phospholipases that facilitate membrane fusion and exocytosis of MMP-9. Conclusions: This work suggests that these regulatory lipids and associated effector proteins are locally synthesized and/or recruited to exocytic sites, during the time of membrane fusion and cargo release, and their enrichment at fusion sites serves as an important spatial and temporal organizing “element” defining individual exocytic sites.

show abstract

Section: Pma-supporting

confidence: 89%

Imaging the rapid yet transient accumulation of regulatory lipids, lipid kinases, and protein kinases during membrane fusion, at sites of exocytosis of MMP-9 in cancer cells

Stephens

Powell

Taraska

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…2007). Interestingly, a recent study demonstrated that Rab11 can be phosphorylated and activated by PKC (Pavarotti et al . 2012).…”

Section: Discussionmentioning

confidence: 99%

Oestrogen promotes KCNQ1 potassium channel endocytosis and postendocytic trafficking in colonic epithelium

Rapetti-Mauss¹,

O’Mahony²,

Sepúlveda³

et al. 2013

The Journal of Physiology

View full text Add to dashboard Cite

Key points• Oestrogen (E 2 ) exposure leads to a decrease in both Cl − secretion and KCNQ1 current. This inhibition is maintained by a rapid and sustained retrieval of the channel from the plasma membrane.• The E 2 -stimulated internalization of KCNQ1 occurs via a dynamin-and clathrin-dependent mechanism.• KCNQ1 is recycled back to the cell membrane via Rab4 and Rab11 rather than being degraded.• The signalling pathway activated by E 2 and leading to KCNQ1 internalization involves a signalling cascade, in which the activation of protein kinase Cδ induces the phosphorylation of AMP-dependent kinase. Oestrogen stimulated an increase in the association of KCNQ1 with the ubiquitin ligase Nedd4.2.• The findings provide evidence for a hormone-stimulated regulation of KCNQ1 surface density in colonic epithelium. Moreover, this study complements the understanding of the mechanisms for E 2 -induced inhibition of KCNQ1 previously described, and provides new insights on hormonal regulation of ion channel retrieval from the plasma membrane.Abstract The cAMP-regulated potassium channel KCNQ1:KCNE3 plays an essential role in transepithelial Cl − secretion. Recycling of K + across the basolateral membrane provides the driving force necessary to maintain apical Cl − secretion. The steroid hormone oestrogen (17β-oestradiol; E 2 ), produces a female-specific antisecretory response in rat distal colon through the inhibition of the KCNQ1:KCNE3 channel. It has previously been shown that rapid inhibition of the channel conductance results from E 2 -induced uncoupling of the KCNE3 regulatory subunit from the KCNQ1 channel pore complex. The purpose of this study was to determine the mechanism required for sustained inhibition of the channel function. We found that E 2 plays a role in regulation of KCNQ1 cell membrane abundance by endocytosis. Ussing chamber experiments have shown that E 2 inhibits both Cl − secretion and KCNQ1 current in a colonic cell line, HT29cl.19A, when cultured as a confluent epithelium. Following E 2 treatment, KCNQ1 was retrieved from the plasma membrane by a clathrin-mediated endocytosis, which involved the association between KCNQ1 and the clathrin adaptor, AP-2. Following endocytosis, KCNQ1 was accumulated in early endosomes. Following E 2 -induced endocytosis, rather than being degraded, KCNQ1 was recycled by a biphasic mechanism involving Rab4 and Rab11. Protein kinase Cδ and AMP-dependent kinase were rapidly phosphorylated in response to E 2 on their activating phosphorylation sites, Ser643 and Thr172, respectively (as previously shown). Both kinases are necessary for the E 2 -induced endocytosis, because E 2 failed to induce KCNQ1 internalization following pretreatment with specific inhibitors of both protein kinase Cδ and AMP-dependent kinase. The ubiquitin ligase Nedd4.2 binds KCNQ1 in response to E 2 to induce channel internalization. This study has provided the first demonstration of hormonal regulation of KCNQ1 trafficking. In conclusion, we propose that internalization of KCNQ1 is a key event in th...

show abstract

“…Rab11 is required for bile canalicular formation in WIF‐B9 cells, regulates canalicular localization of BSEP, and mediates TUDC‐ and cAMP‐induced translocation of MRP2 to the PM . Because Rab11 activation involves PKC‐mediated phosphorylation, and cAMP and TUDC activate nPKCδ and cPKCα, respectively, it can be speculated that phosphorylation (and activation) of Rab11 by cPKCα and nPKCδ may be involved in MRP2 translocation to the PM. Further studies are needed to establish a role for Rab11 phosphorylation by PKCs in MRP2 translocation.…”

Section: Beyond Pkc Isoformsmentioning

confidence: 99%

Role of protein kinase C isoforms in bile formation and cholestasis

Anwer

2014

Hepatology

View full text Add to dashboard Cite

Transhepatic solute transport provides the osmotic driving force for canalicular bile formation. Choleretic and cholestatic agents affect bile formation, in part, by altering plasma membrane localizations of transporters involved in bile formation. These short-term dynamic changes in transporter location are highly regulated post-translational events requiring various cellular signaling pathways. Interestingly, both choleretic and cholestatic agents activate the same intracellular signaling kinases, such as phosphoinositide-3-kinase (PI3K), protein kinase C (PKC) and mitogen activated protein kinase (MAPK). An emerging theme is that choleretic and cholestatic effects may be mediated via different isoforms of these kinases. This is most evident for PKC-mediated regulation of plasma membrane localization of NTCP and MRP2 by conventional PKCα (cPKCα), novel PKCδ (nPKCδ), nPKCε, and atypical PKCζ (aPKCζ). Atypical PKCζ may mediate choleretic effects by inserting NTCP into the plasma membrane and nPKCε may mediate cholestatic effects by retrieving MRP2 from the plasma membrane. On the other hand, cPKCα and nPKCδ may be involved in choleretic, cholestatic and anticholestatic effects by inserting, retrieving and inhibiting retrieval of transporters, respectively. The effects of PKC isoforms may be mediated via phosphorylation of the transporters, actin binding proteins (radixin and MARCKS) and Rab proteins. Human NTCP plays an important role in the entry of hepatitis B and D viruses into hepatocytes and consequent infection. Thus, PKCs by regulating NTCP trafficking may also play an important role in hepatic viral infections.

show abstract

Rab11 is phosphorylated by classical and novel protein kinase C isoenzymes upon sustained phorbol ester activation

Abstract: This report shows for the first time that Rab11 is differentially phosphorylated by distinct PKC isoenzymes and that this post-translational modification might be a regulatory mechanism of intracellular trafficking.

Cited by 25 publications

References 47 publications

Imaging the rapid yet transient accumulation of regulatory lipids, lipid kinases, and protein kinases during membrane fusion, at sites of exocytosis of MMP-9 in cancer cells

Imaging the rapid yet transient accumulation of regulatory lipids, lipid kinases, and protein kinases during membrane fusion, at sites of exocytosis of MMP-9 in cancer cells

Oestrogen promotes KCNQ1 potassium channel endocytosis and postendocytic trafficking in colonic epithelium

Role of protein kinase C isoforms in bile formation and cholestasis

Contact Info

Product

Resources

About