Prolactin receptor signal transduction in cells of the immune system

Cv, Clevenger; Freier, DO; Kline, J. Bradford

doi:10.1677/joe.0.1570187

Cited by 117 publications

(57 citation statements)

References 94 publications

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“…Jurkat cells turned out to be insensitive to apoptosis induced by corticosteroids, and it was not possible to evaluate effects of PRL on dexamethasone-induced apoptosis. Instead, our results showed that in the presence of dexamethasone, PRL was no longer able to prevent starvation-induced apoptosis (data not shown), confirming previously reported antagonistic effects of dexamethasone on PRL activity (Clevenger et al, 1998).…”

Section: Prolactin and Apoptosis Induction In Jurkat Cellssupporting

confidence: 90%

“…Prolactin modulates functions of the immune system by stimulating cell proliferation and prolonging cell survival (Clevenger et al, 1998). Several in vitro studies have suggested that exogenous PRL can act as a comitogen for Concanavalin A (Con A)-stimulated splenocytes (Montgomery et al, 1987), IL-2-stimulated L2 T cells (Clevenger et al, 1990) and human peripheral blood lymphocytes (Matera et al, 1992).…”

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confidence: 99%

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Role of prolactin receptor and CD25 in protection of circulating T lymphocytes from apoptosis in patients with breast cancer

et al. 2003

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Prolactin (PRL) has been reported to inhibit apoptosis in various cell types and to serve as a cofactor in the upregulation of CD25 on T cells during activation. We investigated a possible relation between prolactin receptor (PRL-R) or IL-2 receptor alpha (IL-2Ra, CD25) expression on circulating T lymphocytes and their apoptosis in patients with breast cancer. Peripheral blood mononuclear cells obtained from 25 patients, 25 normal controls (NC) and three cord blood samples were evaluated for Annexin V binding and expression of CD95, CD25, and PRL-R on CD3 + T cells by multicolour flow cytometry. Plasma levels of PRL, sCD95L, and sIL-2R were determined in patients and controls and related to T-cell apoptosis. The ability of PRL to protect T cells from apoptosis induced by various agents was also studied. Expression of PRL-R on the surface of T cells was comparable in patients with breast cancer and NC, but PRL plasma levels in patients were significantly lower (Po0.05). In patients, 18711% (mean7s.d.) of CD3 + cells bound Annexin V, compared to 976% in NC (Po0.0004). Percentages of CD3 + Fas + and CD3 + CD25 + cells were higher in the peripheral circulation of patients than NC (Po0.0001 and o0.04, respectively). Levels of sFasL were lowest in plasma of the patients with the highest proportions of CD3 + Fas + T cells. Most T cells undergoing apoptosis were CD3 + CD25 À in patients, and the proportion of CD3 + CD25 À Annexin V + cells was significantly increased in patients compared to NC (Po0.006). Ex vivo PRL protected T cells from starvation-induced or anti-CD3Ab-induced but not from Fas/FasL-dependent apoptosis. These results indicate that expression of CD25 but not of PRL-R on the surface of activated T lymphocytes appears to be involved in modulating Fas/Fas -ligand interactions, which are, in part, responsible for apoptosis of T lymphocytes and excessive turnover of immune cells in the circulation of patients with breast cancer.

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Section: Prolactin and Apoptosis Induction In Jurkat Cellssupporting

confidence: 90%

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confidence: 99%

Role of prolactin receptor and CD25 in protection of circulating T lymphocytes from apoptosis in patients with breast cancer

et al. 2003

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“…PRL, in addition to its endocrine influence on the immune system, acts as a cytokine released within the immune system regulating lymphogenic responses (Matera 1996, Clevenger et al 1998. Moreover, it has been shown that stress in early pregnancy is able to diminish the secretion of progesterone and PRL, which in turn may alter the pregnancy protective cytokine and immune cell milieu (Arck et al 2008, Parker & Douglas 2010.…”

Section: Implantationmentioning

confidence: 99%

Prolactin secretion patterns: basic mechanisms and clinical implications for reproduction

Egli¹,

Leeners²,

Krüger³

2010

Reproduction

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Prolactin (PRL) is one of the most versatile hormones in the mammalian body affecting reproductive, sexual, metabolic, immune, and other functions. It is therefore not surprising that the neural control of PRL secretion is complex, involving the coordinated actions of several hypothalamic nuclei. A plethora of experimental data exists on the hypothalamic control of hormone secretion under various physiological stimuli. There have been even mathematical models and computer studies published, which help to understand the complex hypothalamic-pituitary network. Nevertheless, the putative role of PRL for human reproduction still has to be clarified. Here, we review data on the underlying mechanisms controlling PRL secretion using both experimental and mathematical approaches. These investigations primarily focus on rhythmic secretion in rats during early pregnancy or pseudopregnancy, and they point to the important role of oxytocin as a crucial PRL-releasing factor. Recent data on human studies and their theoretical and clinical implications are reviewed as well. In particular, studies demonstrating a sustained PRL surge after sexual climax in males and females are presented, indicating possible implications for both sexual satiation and reproductive functions. Taking these data together, there is evidence for the hypothesis that the PRL surge induced by sexual activity, together with the altered PRL rhythmic pattern, is important for successful initialization of pregnancy not only in rodents but also possibly in humans. However, further investigations are needed to clarify such a role in humans.

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“…The prolactin receptor (PRLr) is a member of the cytokine receptor superfamily that transduces the signals of the pituitary hormone PRL, which is implicated in numerous biological functions (including mammary gland development and lactation) and plays an important role in mammary tumorigenesis (Bole-Feysot et al 1998, Clevenger et al 1998, Goffin et al 2002, Vera-Lastra et al 2002. The fine-tuning of PRL signaling is achieved by balancing/counter-balancing PRL-generated signals with concomitant down-modulation of PRLr, which limits availability of the receptor on the surface to bind PRL (Djiane et al 1979(Djiane et al , 1981.…”

Section: Introductionmentioning

confidence: 99%

Prolactin stimulates ubiquitination, initial internalization, and degradation of its receptor via catalytic activation of Janus kinase 2

Swaminathan

Varghese²,

Thangavel³

et al. 2007

Journal of Endocrinology

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Prolactin (PRL) activates its receptor to initiate signal transduction pathways (including activation of Janus kinases, Jak) but also stimulates downregulation of this receptor to limit the magnitude and duration of signaling. Degradation of the long form of PRL receptor (PRLr) depends on its phosphorylation on Ser349 that is required to facilitate PRLr ubiquitination. Signaling events that mediate PRL-induced degradation of PRLr remain to be elucidated. Here, we investigated the role of Jak2 activity in ligand-triggered increase of PRLr phosphorylation on Ser349, PRLr ubiquitination, endocytosis, and degradation. Using Jak2 reconstitution in Jak2-null cells as well as pharmacologic approaches, we found that treatment with PRL (but not with PRLr antagonist) promotes phosphorylation of PRLr on Ser349 and accelerates endocytosis of PRLr. Furthermore, PRL-stimulated PRLr phosphorylation, endocytosis, and degradation in Jak2-null cells reconstituted with wild type but not with catalytically inactive Jak2. We discuss how Jak2-mediated signaling might be transduced into Ser349 phosphorylation of PRLr as well as its ubiquitination and endocytosis.

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Prolactin receptor signal transduction in cells of the immune system

Cited by 117 publications

References 94 publications

Role of prolactin receptor and CD25 in protection of circulating T lymphocytes from apoptosis in patients with breast cancer

Role of prolactin receptor and CD25 in protection of circulating T lymphocytes from apoptosis in patients with breast cancer

Prolactin secretion patterns: basic mechanisms and clinical implications for reproduction

Prolactin stimulates ubiquitination, initial internalization, and degradation of its receptor via catalytic activation of Janus kinase 2

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