Activation of L‐arginine transport by protein kinase C in rabbit, rat and mouse alveolar macrophages

Racké, Kurt; Hey, Claudia; Mössner, Jutta; Hammermann, Rainer; Stichnote, Christina; Wessler, Ignaz

doi:10.1111/j.1469-7793.1998.813bg.x

Cited by 31 publications

(27 citation statements)

References 40 publications

(40 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the increased CAT-1 mRNA in EA.hy926 cells is not translated into protein, this might be different in other cell types or under different experimental conditions, particularly because translation of the CAT-1 mRNA is extensively controlled by nutrient supply (12). However in rat, rabbit, and mouse peritoneal macrophages, a fast up-regulation of system y ϩ activity independent of protein synthesis has been observed, suggesting activation or cell surface recruitment of pre-existing transporter protein (33). The abundance of hCAT-1 in intracellular membranes observed in the present study makes the latter mechanism very likely.…”

Section: Discussionmentioning

confidence: 98%

Protein Kinase C Activation Promotes the Internalization of the Human Cationic Amino Acid Transporter hCAT-1

Rotmann

Strand

Martiné

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 98%

Protein Kinase C Activation Promotes the Internalization of the Human Cationic Amino Acid Transporter hCAT-1

Rotmann

Strand

Martiné

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…These studies suggested that CAT-1 phosphorylation affects its functional properties. Earlier work demonstrated an increased cationic amino acid transport activity in macrophages upon long-term PMA treatment, although such up-regulation could involve transporters other than CAT-1 (46). The work by Rotmann and co-workers (7,47) demonstrated that the PKC-induced decrease in CAT-1 activity is due to down-regulation of the cell surface CAT-1.…”

Section: Discussionmentioning

confidence: 99%

Protein Kinase C-dependent Ubiquitination and Clathrin-mediated Endocytosis of the Cationic Amino Acid Transporter CAT-1

Viña-Vilaseca

Bender-Sigel

Sorkina

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Cationic amino acid transporter 1 (CAT-1) is responsible for the bulk of the uptake of cationic amino acids in most mammalian cells. Activation of protein kinase C (PKC) leads to downregulation of the cell surface CAT-1. To examine the mechanisms of PKC-induced down-regulation of CAT-1, a functional mutant of CAT-1 (CAT-1-HA-GFP) was generated in which a hemagglutinin antigen (HA) epitope tag was introduced into the second extracellular loop and GFP was attached to the carboxyl terminus. CAT-1-HA-GFP was stably expressed in porcine aorthic endothelial and human epithelial kidney (HEK) 293 cells. Using the HA antibody internalization assay we have demonstrated that PKC-dependent endocytosis was strongly inhibited by siRNA depletion of clathrin heavy chain, indicating that CAT-1-HA-GFP internalization requires clathrin-coated pits. Internalized CAT-1-HA-GFP was accumulated in early, recycling, and late endosomes. PKC activation also resulted in ubiquitination of CAT-1. CAT-1 ubiquitination and endocytosis in phorbol ester-stimulated porcine aorthic endothelial and HEK293 cells were inhibited by siRNA knockdown of NEDD4-2 and NEDD4-1 E3 ubiquitin ligases, respectively. In contrast, ubiquitination and endocytosis of the dopamine transporter was dependent on NEDD4-2 in all cell types tested. Altogether, our data suggest that ubiquitination mediated by NEDD4-2 or NEDD4-1 leading to clathrin-mediated endocytosis is the common mode of regulation of various transporter proteins by PKC. Cationic amino acid transporter (CAT)-12 is a member of the SLC7 gene family of membrane transport proteins. The SLC7 family is divided into two groups, glycosylated (CAT) and nonglycosylated transporters (reviewed in Ref. 1). The latter associate with a glycosylated protein from the SLC3 family to form heteromeric amino acid transporters. There are four proven members in the CAT subfamily: CAT-1, CAT-2A, CAT-2B, and CAT-3 (reviewed in Ref. 2). All CATs have a predicted topology of 14 transmembrane domains with cytoplasmic amino and carboxyl termini. The largest, third extracellular loop is glycosylated in all CATs. CAT-2 proteins are also glycosylated in the second loop. CAT-1 is expressed ubiquitously in all adult tissues except the liver (reviewed in Ref.3). The transport properties of CAT-1 resemble those of system y ϩ , defined by the selectivity for cationic amino acids, K m of 0.1-0.2 mM, Na ϩ and pH independence, and strong trans-stimulation. CAT-1 is ubiquitously expressed and the main portal of entry for cationic amino acids into mammalian cells. Homozygous knockout of CAT-1 in mice is postnatally lethal (4). CAT-1 activity has been reported to be regulated through activation of protein kinase C (PKC) (5, 6). Even though there are some discrepancies, most studies conclude that activation of PKC leads to inhibition of L-Arg uptake due to the decreased activity of CAT-1. Studies of CAT-1 phosphorylation and mutations of the PKC phosphorylation consensus sites in CAT-1 suggested that CAT-1 inhibition by PKC is not due to CAT-1 phosp...

show abstract

“…For example, in human hepatoma cells (5), in human endothelial EA.hy926 cells (13), and in oocytes expressing the CAT-1 transporter (13), PMA induced inhibition of L-arginine uptake, whereas in macrophages (15,29), human umbilical vein endothelial cells (27), and Caco-2 intestinal epithelial cells (26), PMA activated L-arginine uptake. The differences in the effects of PMA reported by these groups can be explained by different duration of treatment with PMA or by different permeability or sensitivity of the different cell types to PMA or by different expression of various PKC isoforms in the different cell types.…”

Section: Discussionmentioning

confidence: 99%

“…The possible involvement of PKC in the regulation of the L-arginine transporters in different cell types has been discussed for the last several years (5,13,15,27,29,37). There are two lines of evidence suggesting that PKC may participate in the regulation of CAT-1 activity.…”

Section: Discussionmentioning

confidence: 99%

Classical isoforms of PKC as regulators of CAT-1 transporter activity in pulmonary artery endothelial cells

Krotova

Zharikov

Block

2003

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

Activation of L‐arginine transport by protein kinase C in rabbit, rat and mouse alveolar macrophages

Cited by 31 publications

References 40 publications

Protein Kinase C Activation Promotes the Internalization of the Human Cationic Amino Acid Transporter hCAT-1

Protein Kinase C Activation Promotes the Internalization of the Human Cationic Amino Acid Transporter hCAT-1

Protein Kinase C-dependent Ubiquitination and Clathrin-mediated Endocytosis of the Cationic Amino Acid Transporter CAT-1

Classical isoforms of PKC as regulators of CAT-1 transporter activity in pulmonary artery endothelial cells

Contact Info

Product

Resources

About