Post‐transcriptional regulation of the transferrin receptor and 4F2 antigen heavy chain mRNA during growth activation of spleen cells

Teixeira, Santuza Maria Ribeiro; Kühn, Lukas C.

doi:10.1111/j.1432-1033.1991.tb16438.x

Cited by 39 publications

(22 citation statements)

References 70 publications

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“…Although its function remains unknown, this protein has been proposed to be involved in the modulation of intracellular Ca2+ levels (23). The expression of 4F2 antigen is known to be highly regulated at the onset of cell proliferation (16,24,25). In this study we demonstrate that human 4F2hc (12) 1992) of an amino acid transport system, we measured the uptake of isotopically labeled amino acids by oocytes injected with cRNA prepared by in vitro transcription of 4F2hc cDNA.…”

mentioning

confidence: 69%

Stimulation of system y(+)-like amino acid transport by the heavy chain of human 4F2 surface antigen in Xenopus laevis oocytes.

Bertran

Magagnin

Werner

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

140

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A kidney cortex cDNA clone (rBAT) has recently been isolated, which upon in vitro transcription and capping complementary RNA (cRNA) and injection into Xenopus laevis oocytes induces a system b0°'-like amino acid transport activity. This cDNA encodes a type II membrane glycoprotein that shows significant homology to another type II membrane glycoprotein, the heavy chain of the human and mouse 4F2 surface antigen (4F2hc). Here we demonstrate that injection of human 4F2hc cRNA into oocytes results in the activation of a cation-preferring amino acid transport system that appears to be identical to the y+-like transport already present in the oocyte. This is based on the following results: (i) Injection of in vitro transcripts from 4F2hc cDNA (4F2hc cRNA) into oocytes stimulates up to 10-fold the sodium-independent uptake of L-arginine and up to 4.1-fold the sodium-dependent uptake of L-leucine. In contrast, 4F2hc cRNA does not increase the basal sodium-independent uptake of L-leucine. (ii) Basal and 4F2hc cRNA-stimulated sodium-independent uptake of L-arginine is completely inhibited by L-leucine in the presence of sodium. Similarly, the basal and 4F2hc cRNA-stimulated sodium-dependent uptake of L-leucine is entirely inhibited by L-arginine. (Mi) The stimulation of sodium-independent uptake of L-arge and the stimulation of sodium-dependent uptake of L-leucine induced by injection of 4F2hc cRNA are both completely inhibited by dibasic L amino acids and to a lesser extent by D-ornithine. (iv) Both basal and 4F2hc cRNA-stimulated sodium-independent uptake of L-arginine show two additional characteristics of the system y+ transport activity: inhibition of L-arginine uptake by L-homoserine only in the presence of sodium and an increase in the inhibition exerted by L-histidine as the extracellular pH decreased. Our results allow us to propose that an additional family of type II membrane glycoproteins (composed by rBAT and 4F2hc) is involved in amino acid transport, either as specific activators or as components of amino acid transport systems.Amino acids cross the plasma membrane of cells via sodiumindependent and sodium-dependent carriers. In eukaryotic cells, several carriers have been defined based on ion dependency, substrate specificity, and kinetic properties (1). Our knowledge of the structural identity of these carriers is limited. Recently, two cDNAs related to amino acid transport activity in mammalian cells have been isolated: (i) The murine receptor for the ecotropic murine leukemia virus has been identified as being responsible for system y+, a sodiumindependent cation-preferring amino acid carrier (2, 3). (ii) As described in the two preceding papers, kidney cortex cDNAs from rabbit and rat [named rBAT (b°+ amino acid transporter-related protein) (4) and D2 (5), respectively] have been cloned, which upon injection into oocytes induce system b°+ (6), a sodium-independent carrier for cationic and neutral amino acids (including L-cystine). The predicted protein for the ecotropic murine leukemia vir...

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mentioning

confidence: 69%

Stimulation of system y(+)-like amino acid transport by the heavy chain of human 4F2 surface antigen in Xenopus laevis oocytes.

Bertran

Magagnin

Werner

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

140

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“…These observations suggest that LAT1 plays a role in the uptake of amino acids required for growth and proliferation. Correspondingly, 4F2hc has also been shown to be strongly induced at the mRNA and protein levels in cell proliferation (13)(14)(15). Furthermore, 4F2hc mRNA accumulation observed in activated lymphocytes results from a post-transcriptional regulation (15).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the glycoproteins may regulate the surface expression of the transporters. 4F2hc mRNA is strongly induced in cell proliferation (13)(14)(15) and expressed in numerous tissues (16). 4F2 antigen was originally described in dividing T cells as an activation antigen composed of a heavy chain and a disulfide-linked light chain (17,18).…”

mentioning

confidence: 99%

LAT2, a New Basolateral 4F2hc/CD98-associated Amino Acid Transporter of Kidney and Intestine

Rossier¹,

Meier²,

Bauch³

et al. 1999

Journal of Biological Chemistry

329

315

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Glycoprotein-associated amino acid transporters (gpaAT) are permease-related proteins that require heterodimerization to express their function. So far, four vertebrate gpaATs have been shown to associate with 4F2hc/CD98 for functional expression, whereas one gpaAT specifically associates with rBAT. In this study, we characterized a novel gpaAT, LAT2, for which mouse and human cDNAs were identified by expressed sequence tag data base searches. The encoded ortholog proteins are 531 and 535 amino acids long and 92% identical. They share 52 and 48% residues with the gpaATs LAT1 and y ؉ LAT1, respectively. When mouse LAT2 and human 4F2hc cRNAs were co-injected into Xenopus oocytes, disulfide-linked heterodimers were formed, and an L-type amino acid uptake was induced, which differed slightly from that produced by LAT1-4F2hc: the apparent affinity for L-phenylalanine was higher, and L-alanine was transported at physiological concentrations. In the presence of an external amino acid substrate, LAT2-4F2hc also mediated amino acid efflux. LAT2 mRNA is expressed mainly in kidney and intestine, whereas LAT1 mRNA is expressed widely. Immunofluorescence experiments showed colocalization of 4F2hc and LAT2 at the basolateral membrane of kidney proximal tubules and small intestine epithelia. In conclusion, LAT2 forms with LAT1 a subfamily of L-type gpaATs. We propose that LAT1 is involved in cellular amino acid uptake, whereas LAT2 plays a role in epithelial amino acid (re)absorption.

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“…This situation could occur during monocytic or erythropoietic differentiation and cell proliferation. These circumstances require increased levels of cellular iron concomitant with an increase in IRE binding activity needed for the accumulation of TfR mRNA (39)(40)(41)(42)(43). The ability to differentially regulate IRP activity independently of cellular iron status is crucial to the normal progression of such processes.…”

Section: Discussionmentioning

confidence: 99%

Novel role of phosphorylation in Fe–S cluster stability revealed by phosphomimetic mutations at Ser-138 of iron regulatory protein 1

Brown

Anderson²,

Steffen³

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

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Animals regulate iron metabolism largely through the action of the iron regulatory proteins (IRPs). IRPs modulate mRNA utilization by binding to ironresponsive elements (IRE) in the 5 or 3 untranslated region of mRNAs encoding proteins involved in iron homeostasis or energy production. IRP1 is also the cytosolic isoform of aconitase. The activities of IRP1 are mutually exclusive and are modulated through the assembly͞disassembly of its [4Fe-4S] cluster, reversibly converting it between an IRE-binding protein and cytosolic aconitase. IRP1 is also phosphoregulated by protein kinase C, but the mechanism by which phosphorylation posttranslationally increases IRE binding activity has not been fully defined. To investigate this, Ser-138 (S138), a PKC phosphorylation site, was mutated to phosphomimetic glutamate (S138E), aspartate (S138D), or nonphosphorylatable alanine (S138A). The S138E IRP1 mutant and, to a lesser extent, the S138D IRP1 mutant were impaired in aconitase function in yeast when grown aerobically but not when grown anaerobically. Purified wild-type and mutant IRP1s could be reconstituted to active aconitases anaerobically. However, when exposed to oxygen, the [4Fe-4S] cluster of the S138D and S138E mutants decayed 5-fold and 20-fold faster, respectively, than was observed for wild-type IRP1. Our findings suggest that stability of the Fe-S cluster of IRP1 can be regulated by phosphorylation and reveal a mechanism whereby the balance between the IRE binding and [4Fe-4S] forms of IRP1 can be modulated independently of cellular iron status. Furthermore, our results show that IRP1 can function as an oxygen-modulated posttranscriptional regulator of gene expression.

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Post‐transcriptional regulation of the transferrin receptor and 4F2 antigen heavy chain mRNA during growth activation of spleen cells

Cited by 39 publications

References 70 publications

Stimulation of system y(+)-like amino acid transport by the heavy chain of human 4F2 surface antigen in Xenopus laevis oocytes.

Stimulation of system y(+)-like amino acid transport by the heavy chain of human 4F2 surface antigen in Xenopus laevis oocytes.

LAT2, a New Basolateral 4F2hc/CD98-associated Amino Acid Transporter of Kidney and Intestine

Novel role of phosphorylation in Fe–S cluster stability revealed by phosphomimetic mutations at Ser-138 of iron regulatory protein 1

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