Implication of alpha4 phosphoprotein and the rapamycin-sensitive mammalian target-of-rapamycin pathway in prolactin receptor signalling.

  title={Implication of alpha4 phosphoprotein and the rapamycin-sensitive mammalian target-of-rapamycin pathway in prolactin receptor signalling.},
  author={R. Boudreau and S. M. Sangster and L. M. Johnson and S. Dauphinee and A. Li and C. K. Too},
  journal={The Journal of endocrinology},
  volume={173 3},
A prolactin (PRL)-responsive 3'-end cDNA encoding rat alpha4 phosphoprotein was previously isolated from a rat lymphoma cDNA library. Rat alpha4 is a homologue of yeast Tap42 and is a component of the mammalian target-of-rapamycin (mTOR) signalling pathway that stimulates translation initiation and G1 progression in response to nutrients and growth factors. In the present study, the full-length rat alpha4 cDNA was obtained by 5'-RACE and the 1023 bp open reading frame predicted a 340 amino acid… Expand
Overexpression of the mTOR alpha4 phosphoprotein activates protein phosphatase 2A and increases Stat1α binding to PIAS1
E ectopic alpha4 increased PP2A activity in COS-1 cells and this was accompanied by Stat1 alpha hypomethylation and increased Stat1alpha-PIAS1 association, which would inhibit Stat action and ultimately inhibit PRL-inducible IRF-1 promoter activity. Expand
α4 phosphoprotein interacts with EDD E3 ubiquitin ligase and poly(A)‐binding protein
A physical interaction between α4 and EDD was shown in rat Nb2 T‐lymphoma and human MCF‐7 breast cancer cell lines, suggesting its involvement in multiple steps in the mTOR pathway that leads to translation initiation and cell‐cycle progression. Expand
Progestin-inducible EDD E3 ubiquitin ligase binds to α4 phosphoprotein to regulate ubiquitination and degradation of protein phosphatase PP2Ac
This study showed induction of the EDD protein by progesterone, 17β-estradiol and prolactin in breast cancer cells, implicating hormone-inducible EDD in PP2Ac turnover. Expand
Characterization of a novel, cytokine-inducible carboxypeptidase D isoform in haematopoietic tumour cells.
A cytokine-inducible CPD-N is selectively expressed in several haematopoietic tumour cells and is inhibited non-competitively by zinc chelator 1,10-phenanthroline and competitively by peptidomimetic inhibitor DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid. Expand
Role of Prolactin Receptors in Lymphangioleiomyomatosis
It is proposed that Prl exerts growth-stimulatory effects on LAM cells, and that antagonizing the Prl receptor can block such effects. Expand
Characterising the signalling mechanism of the mTOR-dependent phosphatase
Results indicate that phosphatase activity is critical in regulation of mTORC1, reflecting the mechanism in yeast and indicates that PP2ABa may be negatively regulated by ubiquitin-mediated proteasomal degradation of Ba in an m TORC1-specific manner. Expand
Prolactin Signaling Pathways Determining Its Direct Effects on Kidneys in the Cholestasis of Pregnancy Model
Direct impact of prolactin on the kidney has been demonstrated and expression of pSTAT5, a key mediator of the long PrlR isoform signaling, was increased in animals with cholestasis of pregnancy. Expand
Role of O‐linked β‐N‐acetylglucosamine modification in the subcellular distribution of alpha4 phosphoprotein and Sp1 in rat lymphoma cells
It was shown that alpha4 and Sp1 contained O‐GlcNAc moieties, which contributed to their nuclear targeting in Nb2 cells, and a 50% downregulation of OGT gene expression by small interfering RNA contributed to its nuclear targeting. Expand
mTOR signaling in lymphangioleiomyomatosis.
  • A. Kristof
  • Biology, Medicine
  • Lymphatic research and biology
  • 2010
Recent scientific findings reviewed here have greatly improved the understanding of mTOR signaling mechanisms, provided new insights into the control of cell growth and proliferation, and facilitated the development of new therapeutic approaches in LAM, as well as other neoplastic disorders that exhibit excessive mTOR activity. Expand


Differential expression of elongation factor-2, α4 phosphoprotein and Cdc5-like protein in prolactin-dependent/independent rat lymphoid cells
  • C. K. Too
  • Medicine, Biology
  • Molecular and Cellular Endocrinology
  • 1997
The differential display of mRNAs technique was used to identify genes which are differentially expressed in the prolactin (PRL)-dependent Nb2-11C and PRL-independent Nb 2-Sp rat lymphoma cell lines and may permit insights into the molecular changes that are involved in regulating the transition to growth factor independence in lymphoid tumors. Expand
Prolactin induces rapid phosphorylation and activation of prolactin receptor-associated RAF-1 kinase in a T-cell line.
It is demonstrated here that PRL induced the phosphorylation of the p72-74 serine/threonine kinase c-Raf-1 in the PRL-dependent rat T-cell line Nb2, demonstrating for the first time an association between thePRL receptor and a serine-threonin kinase affiliated with signal transduction. Expand
Identification and nuclear localization of a novel prolactin and cytokine-responsive carboxypeptidase D.
Curiously, CPD transcripts were low or undetectable in male rat liver but readily detected in female liver, suggesting that sex-specific hormone levels may regulate its expression. Expand
Interleukin 2 and a lactogen regulate proliferation and protein phosphorylation in Nb2 cells.
The results suggest that hGH and IL-2 act through separate receptors to stimulate proliferation of Nb2 cells, and that some of the actions of both mitogens may be mediated, in part, through regulation of protein phosphorylation. Expand
Prolactin, interleukin-2 and FGF-2 stimulate expression, nuclear distribution and DNA-binding of rat homolog of pombe Cdc5 in Nb2 T lymphoma cells
Rapid activation of Cdc5 in response to mitogenic and non-mitogenic stimuli suggests a complex role for CDC5 in cellular regulation and this may not be restricted to mitotic entry or G2/M progression as previously supposed. Expand
A direct linkage between the phosphoinositide 3-kinase-AKT signaling pathway and the mammalian target of rapamycin in mitogen-stimulated and transformed cells.
It is demonstrated that interleukin-3 stimulation induces a wortmannin-sensitive increase in mTOR kinase activity in a myeloid progenitor cell line, and that the activation status of the PI3K-AKT pathway in cancer cells may be an important determinant of cellular sensitivity to the cytostatic effect of rapamycin. Expand
Association of 2',5'-oligoadenylate synthetase with the prolactin (PRL) receptor: alteration in PRL-inducible stat1 (signal transducer and activator of transcription 1) signaling to the IRF-1 (interferon-regulatory factor 1) promoter.
A novel interaction of OAS with the PRL-R is demonstrated and a role for OAS in modulating Stat1-mediated signaling to an immediate early gene promoter is suggested, suggesting that OAS may have additional effects on cytokine receptor signal transduction pathways. Expand
B cell receptor-associated protein alpha4 displays rapamycin-sensitive binding directly to the catalytic subunit of protein phosphatase 2A.
The results reveal a novel heterodimer alpha4-C form of PP2A that may be involved in rapamycin-sensitive signaling pathways in mammalian cells. Expand
PTP1D is a positive regulator of the prolactin signal leading to beta‐casein promoter activation.
The dominant negative inhibitory effect of a phosphatase‐deficient mutant on expression of a beta‐casein promoter‐controlled reporter gene is evidence for an essential role of fully functional PTP1D in the regulation of milk protein gene transcription. Expand
Activation of receptor-associated tyrosine kinase JAK2 by prolactin.
It is proposed that binding of ligand to the PRL receptor activates preassociated JAK2, and that this enzyme generates the initial signal in the intracellular communication cascade. Expand