Leptin receptor activation increases Sam68 tyrosine phosphorylation and expression in human trophoblastic cells

Sánchez-Jiménez, Flora; Pérez-Pérez, Antonio; González-Yanes, Carmen; Najib, Souad; Varone, Cecilia; Sánchez-Margalet, Vı́ctor

doi:10.1016/j.mce.2010.10.014

Cited by 14 publications

(13 citation statements)

References 60 publications

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“…This may be relevant both physiologically and pathophysiologically since a decrease in EIF4EBP1 phosphorylation has been recently found in fetuses with intrauterine growth restriction resulting from impaired placental development [94]. Recently, we have described the participation of the RNA binding protein Sam68 in leptin signaling in human trophoblastic cells, mediating the growth promoting effect of leptin [97,98]. Concentrations of leptin in human cord blood correlate with placental size.…”

Section: Role Of Leptin In Placentationmentioning

confidence: 94%

Role of leptin in female reproduction

Pérez-Pérez

Sánchez-Jiménez

Maymó

et al. 2015

Clinical Chemistry and Laboratory Medicine (CCLM)

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125

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Abstract:Reproductive function is dependent on energy resources. The role of weight, body composition, fat distribution and the effect of diet have been largely investigated in experimental female animals as well as in women. Any alteration in diet and/or weight may induce abnormalities in timing of sexual maturation and fertility. However, the cellular mechanisms involved in the fine coordination of energy balance and reproduction are largely unknown. The brain and hypothalamic structures receive endocrine and/or metabolic signals providing information on the nutritional status and the degree of fat stores. Adipose tissue acts both as a store of energy and as an active endocrine organ, secreting a large number of biologically important molecules termed adipokines. Adipokines have been shown to be involved in regulation of the reproductive functions. The first adipokine described was leptin. Extensive research over the last 10 years has shown that leptin is not only an adipose tissue-derived messenger of the amount of energy stores to the brain, but also a crucial hormone/cytokine for a number of diverse physiological processes, such as inflammation, angiogenesis, hematopoiesis, immune function, and most importantly, reproduction. Leptin plays an integral role in the normal physiology of the reproductive system with complex interactions at all levels of the hypothalamic-pituitary gonadal (HPG) axis. In addition, leptin is also produced by placenta, where it plays an important autocrine function. Observational studies have demonstrated that states of leptin excess, deficiency, or resistance can be associated with abnormal reproductive function. This review focuses on the leptin action in female reproduction.

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Section: Role Of Leptin In Placentationmentioning

confidence: 94%

Role of leptin in female reproduction

Pérez-Pérez

Sánchez-Jiménez

Maymó

et al. 2015

Clinical Chemistry and Laboratory Medicine (CCLM)

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125

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“…The role of MAPK in regulating trophoblast turnover is well documented in both human and animal systems [43,44,47]. Moreover, it was shown that leptin induces proliferative activity in many human cell types [48][49][50], mainly via MAPK activation [51]. We have demonstrated that leptin promotes proliferation of trophoblast cells by this MAPK pathway [41,52].…”

Section: Leptin and Placentamentioning

confidence: 71%

“…In this context, it is interesting to mention the role of Sam68, an RNA-binding protein originally identified as the substrate of Src during mitosis and a member of the signal transduction and activation of RNA metabolism (STAR) family [54,55]. Leptin stimulates Tyr-phosphorylation of Sam68 in the trophoblast, mediating the dissociation from RNA, suggesting that leptin signaling could modulate RNA metabolism [48,56]. Recent data indicate that microRNAs have a fundamental role in a variety of physiological and pathological processes.…”

Section: Leptin and Placentamentioning

confidence: 99%

Leptin and Gestational Diabetes Mellitus

Guadix¹,

Pérez-Pérez²,

Vilariño-García³

et al. 2020

Gestational Diabetes Mellitus - An Overview With Some Recent Advances

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Emerging research has highlighted the importance of leptin in fetal growth and development, independent of its essential role in the regulation of feeding and energy metabolism. Leptin is now considered an important signaling molecule of the reproductive system, since it regulates the production of gonadotropins, the blastocyst formation and implantation, the normal placentation, as well as the fetoplacental communication. Placental leptin is an important cytokine which regulates placental functions in an autocrine or paracrine manner. Leptin seems to play a crucial role during the first stages of pregnancy as it modulates critical processes like proliferation, protein synthesis, invasion, and apoptosis in placental cells. Furthermore, deregulation of leptin levels has been correlated with the pathogenesis of various disorders associated with reproduction and gestation, including gestational diabetes mellitus (GDM). Due to the relevant incidence of the GDM and the importance of leptin, we decided to review the latest information available about leptin action in normal and GDM pregnancies to support the idea of leptin as an important factor and/or predictor of diverse disorders associated with reproduction and pregnancy.

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“…Thus, Sam68 acts as a scaffold protein in response to activation of membrane-bound receptors and extracellular signaling pathways, such as the T-cell receptor [43,48,50–52], insulin receptor [45,53], leptin receptor [54–57], TNF-alpha [58], EGF [59] or HGF/Met signaling [60]. As happens with other RBPs, the interplay between kinases, Sam68 and target RNAs have been suggested in the dynamic regulation of gene expression according to cell signaling.…”

Section: Role Of Sam68 In Signalingmentioning

confidence: 99%

“…Therefore, in addition to ERK dependent phosphorylation of Sam68, Tyr-phosphorylation was demonstrated to have a role in Sam68 modulating AS, as it was mechanistically shown by Sam68 binding to APC-arm in colorectal tumors [113]. The modulation of Sam68’s role in splicing may explain why that in cancer cells, Sam68 is distributed in the cytoplasm instead of the nucleus and is highly phosphorylated in response to some trophic and mitogenic signals [45,57]. This may lead to a differential regulation of Bcl-x splicing and combined with some other effects, may promote proliferation and metastasis.…”

Section: Sam68 and Alternative Splicingmentioning

confidence: 99%

Role of Sam68 in Post-Transcriptional Gene Regulation

Sánchez-Jiménez

Sánchez-Margalet

2013

IJMS

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The STAR family of proteins links signaling pathways to various aspects of post-transcriptional regulation and processing of RNAs. Sam68 belongs to this class of heteronuclear ribonucleoprotein particle K (hnRNP K) homology (KH) single domain-containing family of RNA-binding proteins that also contains some domains predicted to bind critical components in signal transduction pathways. In response to phosphorylation and other post-transcriptional modifications, Sam68 has been shown to have the ability to link signal transduction pathways to downstream effects regulating RNA metabolism, including transcription, alternative splicing or RNA transport. In addition to its function as a docking protein in some signaling pathways, this prototypic STAR protein has been identified to have a nuclear localization and to take part in the formation of both nuclear and cytosolic multi-molecular complexes such as Sam68 nuclear bodies and stress granules. Coupling with other proteins and RNA targets, Sam68 may play a role in the regulation of differential expression and mRNA processing and translation according to internal and external signals, thus mediating important physiological functions, such as cell death, proliferation or cell differentiation.

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Leptin receptor activation increases Sam68 tyrosine phosphorylation and expression in human trophoblastic cells

Cited by 14 publications

References 60 publications

Role of leptin in female reproduction

Role of leptin in female reproduction

Leptin and Gestational Diabetes Mellitus

Role of Sam68 in Post-Transcriptional Gene Regulation

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