Signaling Receptome: A Genomic and Evolutionary Perspective of Plasma Membrane Receptors Involved in Signal Transduction

Ben‐Shlomo, Izhar; Hsu, Sze-Bi; Rauch, Rami; Kowalski, H. W.; Hsueh, Aaron J. W.

doi:10.1126/stke.2003.187.re9

Cited by 95 publications

(45 citation statements)

References 162 publications

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“…To investigate whether variation in the polypeptide intercellular signaling molecules contribute to physiological diversities in humans, we curated 457 human G-protein-coupled receptors (GPCRs) and their cognate ligand genes as well as 382 human non-GPCR receptor and ligand genes (Supplemental Table 1; Ben-Shlomo et al 2003;Semyonov et al 2008). We started by using the population differentiation statistic F ST to identify the leads for functional characterization (Lewontin and Krakauer 1973;Akey et al 2002;Li et al 2008 1).…”

Section: Resultsmentioning

confidence: 99%

Adaptive selection of an incretin gene in Eurasian populations

Chang

Cai

et al. 2010

Genome Res.

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Diversities in human physiology have been partially shaped by adaptation to natural environments and changing cultures. Recent genomic analyses have revealed single nucleotide polymorphisms (SNPs) that are associated with adaptations in immune responses, obvious changes in human body forms, or adaptations to extreme climates in select human populations. Here, we report that the human GIP locus was differentially selected among human populations based on the analysis of a nonsynonymous SNP (rs2291725). Comparative and functional analyses showed that the human GIP gene encodes a cryptic glucose-dependent insulinotropic polypeptide (GIP) isoform (GIP55S or GIP55G) that encompasses the SNP and is resistant to serum degradation relative to the known mature GIP peptide. Importantly, we found that GIP55G, which is encoded by the derived allele, exhibits a higher bioactivity compared with GIP55S, which is derived from the ancestral allele. Haplotype structure analysis suggests that the derived allele at rs2291725 arose to dominance in East Asians ∼8100 yr ago due to positive selection. The combined results suggested that rs2291725 represents a functional mutation and may contribute to the population genetics observation. Given that GIP signaling plays a critical role in homeostasis regulation at both the enteroinsular and enteroadipocyte axes, our study highlights the importance of understanding adaptations in energy-balance regulation in the face of the emerging diabetes and obesity epidemics.

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Section: Resultsmentioning

confidence: 99%

Adaptive selection of an incretin gene in Eurasian populations

Chang

Cai

et al. 2010

Genome Res.

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“…When trophoblast cells had grown outward from the adhered blastocysts and the primary trophoblast cells became visible, these embryos were designated as outgrowth blastocysts. The proportions of blastocysts undergoing adhesion and outgrowth were estimated at 72 h after growth factor treatment [27], [28]. The proportions of hatched blastocysts showing adhesion or outgrowth were used to estimate the implantation capacity of blastocysts in vitro .…”

Section: Methodsmentioning

confidence: 99%

Promotion of Human Early Embryonic Development and Blastocyst Outgrowth In Vitro Using Autocrine/Paracrine Growth Factors

et al. 2012

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Studies using animal models demonstrated the importance of autocrine/paracrine factors secreted by preimplantation embryos and reproductive tracts for embryonic development and implantation. Although in vitro fertilization-embryo transfer (IVF-ET) is an established procedure, there is no evidence that present culture conditions are optimal for human early embryonic development. In this study, key polypeptide ligands known to be important for early embryonic development in animal models were tested for their ability to improve human early embryo development and blastocyst outgrowth in vitro. We confirmed the expression of key ligand/receptor pairs in cleavage embryos derived from discarded human tri-pronuclear zygotes and in human endometrium. Combined treatment with key embryonic growth factors (brain-derived neurotrophic factor, colony-stimulating factor, epidermal growth factor, granulocyte macrophage colony-stimulating factor, insulin-like growth factor-1, glial cell-line derived neurotrophic factor, and artemin) in serum-free media promoted >2.5-fold the development of tri-pronuclear zygotes to blastocysts. For normally fertilized embryos, day 3 surplus embryos cultured individually with the key growth factors showed >3-fold increases in the development of 6–8 cell stage embryos to blastocysts and >7-fold increase in the proportion of high quality blastocysts based on Gardner’s criteria. Growth factor treatment also led to a 2-fold promotion of blastocyst outgrowth in vitro when day 7 surplus hatching blastocysts were used. When failed-to-be-fertilized oocytes were used to perform somatic cell nuclear transfer (SCNT) using fibroblasts as donor karyoplasts, inclusion of growth factors increased the progression of reconstructed SCNT embryos to >4-cell stage embryos. Growth factor supplementation of serum-free cultures could promote optimal early embryonic development and implantation in IVF-ET and SCNT procedures. This approach is valuable for infertility treatment and future derivation of patient-specific embryonic stem cells.

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“…Because we aimed to identify plasma membrane receptors that were upregulated in TNBC models and associated with TNBC aggressiveness as potential therapeutic targets, our analyses were restricted to 796 membrane surface molecules that are expressed in all human tissues. This list was generated per Castellano et al [42] and updated by a manually curated PubMed search and integration with HPMR [43], with the database provided by Almén [44]; 258 of the 796 unique genes were detected in our breast cancer models.…”

Section: Methodsmentioning

confidence: 99%

CDCP1 is a novel marker of the most aggressive human triple-negative breast cancers

et al. 2016

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CDCP1, a transmembrane noncatalytic receptor, the expression of which has been associated with a poor prognosis in certain epithelial cancers, was found to be expressed in highly aggressive triple-negative breast cancer (TNBC) cell models, in which it promoted aggressive activities—ie, migration, invasion, anchorage-independent tumor growth, and the formation of vascular-like structures in vitro. By immunohistochemical (IHC) analysis of 100 human TNBC specimens, CDCP1 was overexpressed in 57% of samples, 38% of which exhibited a gain in CDCP1 copy number by fluorescence in situ hybridization (FISH). CDCP1 positivity was significantly associated between FISH and IHC. CDCP1 expression and gains in CDCP1 copy number synergized with nodal (N) status in determining disease-free and distant disease-free survival. The hazard ratios (HRs) of the synergies between CDCP1 positivity by IHC and FISH and lymph node positivity in predicting relapse did not differ significantly, indicating that CDCP1 overexpression in human primary TNBCs, regardless of being driven by gains in CDCP1, is for a critical factor in the progression of N-positive TNBCs. Thus, CDCP1 is a novel marker of the most aggressive N-positive TNBCs and a potential therapeutic target.

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Signaling Receptome: A Genomic and Evolutionary Perspective of Plasma Membrane Receptors Involved in Signal Transduction

Cited by 95 publications

References 162 publications

Adaptive selection of an incretin gene in Eurasian populations

Adaptive selection of an incretin gene in Eurasian populations

Promotion of Human Early Embryonic Development and Blastocyst Outgrowth In Vitro Using Autocrine/Paracrine Growth Factors

CDCP1 is a novel marker of the most aggressive human triple-negative breast cancers

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