Affinage

Showing CSH2 — CSB is a alias.

CSH2

Chorionic somatomammotropin hormone 2 · UniProt P0DML3

Length
217 aa
Mass
25.0 kDa
Annotated
2026-06-09
98 papers in source corpus 17 papers cited in narrative 18 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CSH2 (hCS-B/hPL-B) is a placenta-specific member of the human growth hormone/chorionic somatomammotropin gene cluster on chromosome 17, expressed exclusively in placental tissue and restricted from the pituitary despite ~95% sequence identity among the five clustered genes (PMID:2744760). Its high-level, position-independent expression depends on a multicomponent locus control region (LCR) located ~15 and ~30 kb 5' of hGH-N, where DNase I hypersensitive sites shared between pituitary and placenta act synergistically to enforce regulated, tissue-specific output (PMID:8524268). Placenta-specific transcription is driven by a downstream enhancer composed of DF-3 and DF-4 elements: the placenta-restricted factor hTEF-5 binds cooperatively to a tandemly repeated TEF-binding motif within DF-4, and a syncytiotrophoblast-specific protein binds the 3' portion of DF-4, with naturally occurring single-base differences from the paralogous hCS-A enhancer explaining the differential activity between the two genes (PMID:7945936, PMID:8892756, PMID:9148898). C/EBPβ modulates this system, repressing the CSH2 promoter alone but stimulating it in the context of the hCS-B enhancer, and associates with CS-B chromatin in native placenta (PMID:21737519). Access to the LCR and enhancer is gated epigenetically, as combined DNA-demethylation and histone-deacetylase inhibition de-represses CSH2 with concomitant H3/H4 hyperacetylation at the 3' enhancer and LCR (PMID:26634190). The chromosomal architecture linking LCR hypersensitive sites (HS III-V) to the CSH2 promoter is physiologically regulated: it is disrupted by maternal obesity and partially restored by insulin, with PEG3/PW1 binding to the LCR repressing CSH2 and tracking inversely with hPL expression (PMID:29763375). P sequences upstream of the placental genes recruit a forkhead/NF-1 repressor complex that, via LCR HS III contacts, prevents CSH2 expression in the pituitary (PMID:40362658).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1989 High

    Established that CSH2 is a distinct, placenta-restricted member of a highly homologous five-gene cluster, defining the central regulatory problem of how near-identical genes achieve tissue-specific expression.

    Evidence cDNA library screening with gene-specific oligonucleotides and full locus sequencing

    PMID:2744760

    Open questions at the time
    • Does not identify the cis-elements or factors enforcing placental restriction
    • No protein-level characterization
  2. 1991 Medium

    Showed CSH2 is hormonally regulated and produces a ~22 kDa secreted protein, demonstrating a cellular model (BeWo) for inducible expression.

    Evidence Oligonucleotide-specific Northern and Western blotting with T3 treatment of BeWo cells

    PMID:1708334

    Open questions at the time
    • Mechanism of T3 responsiveness at the CSH2 locus not mapped
    • Cell-line restriction (BeWo only) unexplained
  3. 1993 Medium

    Demonstrated that methotrexate selectively suppresses CSH2 and blunts its T3 response without altering T3 receptor levels, indicating regulation acts at the level of locus responsiveness rather than receptor abundance.

    Evidence Northern blotting, T3 receptor binding assay, and MTX treatment of BeWo cells

    PMID:8472847

    Open questions at the time
    • Molecular target of MTX interference not identified
    • No link to specific cis-elements
  4. 1994 Medium

    Localized placenta-specific enhancer activity to DF-3 and DF-4 elements and identified a TEF-1-like motif in DF-4 bound by protein f, establishing the first cis/trans determinants of CSH2 enhancer function.

    Evidence EMSA, UV cross-linking, supershift, and TKCAT reporter assays in JEG-3 cells

    PMID:7945936

    Open questions at the time
    • Identity of protein f not molecularly defined
    • Syncytiotrophoblast-specific factor not yet characterized
  5. 1995 High

    Defined a multicomponent LCR ~15-30 kb upstream as required for high-level, position-independent CSH2 expression, showing that multiple hypersensitive sites act synergistically rather than independently.

    Evidence DNase I chromatin mapping and transgenic mouse integration of cosmid constructs

    PMID:8524268

    Open questions at the time
    • Trans-acting factors at LCR HS sites not identified
    • Mechanism of synergy and promoter selection unresolved
  6. 1996 Medium

    Resolved why CSH2 and hCS-A enhancers differ in strength, attributing it to a single base difference in DF-3 and a syncytiotrophoblast-specific factor at DF-4, and linked enhancer activation to cytotrophoblast-to-syncytiotrophoblast differentiation.

    Evidence Transient expression in primary syncytiotrophoblast culture, EMSA, and site-directed mutagenesis

    PMID:8892756

    Open questions at the time
    • Syncytiotrophoblast-specific factor identity unknown
    • Differentiation signal driving enhancer activation not defined
  7. 1997 High

    Identified hTEF-5 as a placenta-enriched factor binding cooperatively to a tandem TEF element in the CSH2 enhancer, providing a molecular basis for differential enhancer activity via a TEF-5-disrupting mutation in hCS-A.

    Evidence EMSA, anti-TEA-domain supershift, mutagenesis, and cDNA cloning/Northern blotting

    PMID:9148898

    Open questions at the time
    • hTEF-5 not the sole syncytiotrophoblast determinant
    • Cofactors enabling cooperative binding not defined
  8. 1997 Medium

    Distinguished cAMP/PMA responsiveness between paralogs, showing a single-nucleotide difference renders CSH2 unresponsive to cAMP while retaining a shared PMA response, further explaining paralog-specific regulation.

    Evidence Transient reporter assays, EMSA, and Southwestern blotting

    PMID:9134496

    Open questions at the time
    • Identity of the 100 kDa and 47 kDa binding proteins only inferred (CREBP/AP-1 related)
    • Physiological role of CSH2 cAMP-unresponsiveness unclear
  9. 2011 High

    Established C/EBPβ as a context-dependent modulator that represses the CSH2 promoter alone but activates it through the hCS-B enhancer, and confirmed differential C/EBPβ occupancy on CS-B chromatin in native placenta.

    Evidence EMSA, transient reporter assays in JEG-3 cells, and ChIP in human placental chromatin

    PMID:21737519

    Open questions at the time
    • Mechanism converting repression to activation by enhancer context unresolved
    • Interplay with hTEF-5 not tested
  10. 2015 Medium

    Showed that DNA methylation and histone acetylation gate chromatin accessibility at the CSH2 enhancer and LCR, with sequential demethylation then HDAC inhibition de-repressing the gene.

    Evidence qRT-PCR, ChIP for hyperacetylated H3/H4, and luciferase reporter assays with epigenetic inhibitors in JEG-3 cells

    PMID:26634190

    Open questions at the time
    • Specific methylated CpGs controlling accessibility not mapped
    • Order-dependence mechanism not explained
  11. 2018 High

    Linked CSH2 regulation to physiology by showing maternal obesity disrupts the LCR-to-promoter chromosomal architecture and that insulin partially restores it, connecting 3D locus topology to hCS output.

    Evidence Chromosome conformation capture (3C), ChIP for RNA Pol II and C/EBPβ, and qPCR across human placental samples

    PMID:29763375

    Open questions at the time
    • Factor mediating obesity-induced topology change not identified in this study
    • Causal direction between architecture and transcription not fully separable
  12. 2014 Medium

    Demonstrated that CSH2 mRNA in breast cancer is not translated to protein at physiological levels, while exposing widespread non-specificity of commercial hPL antibodies.

    Evidence shRNA knockdown, multiple commercial and custom antibodies, IHC, and qRT-PCR

    PMID:24475273

    Open questions at the time
    • Reason for translational silencing not determined
    • Functional consequence of breast cancer mRNA expression unknown
  13. 2025 Medium

    Identified PEG3/PW1 as a direct repressor binding LCR HS III-V whose occupancy tracks inversely with CSH2 expression across obesity and insulin-treated states, providing a trans-acting factor for the obesity-associated architectural changes.

    Evidence ChIP for PEG3, siRNA knockdown in JEG-3 cells, 3C, and qRT-PCR in stratified human placenta (preprint)

    Open questions at the time
    • Preprint, not peer-reviewed
    • Mechanism by which PEG3 alters LCR topology not defined
  14. 2025 Medium

    Explained pituitary exclusion of CSH2, showing P sequences upstream of the placental genes bind a forkhead/NF-1 repressor complex and contact LCR HS III in pituitary chromatin.

    Evidence Reporter assays in pituitary GC cells, EMSA, and 3C in human pituitary chromatin

    PMID:40362658

    Open questions at the time
    • Direct test on CSH2 promoter (vs hPL-A) limited
    • How P-sequence contacts silence the placental enhancer not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The physiological function of the CSH2 protein product itself, its receptor engagement, and the basis for its translational silencing outside placenta remain uncharacterized in the available corpus.
  • No receptor or signaling pathway defined for the CSH2 protein
  • No structural information
  • Functional role of placental lactogen B distinct from paralogs not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Pathway
R-HSA-74160 Gene expression (Transcription) 8 R-HSA-4839726 Chromatin organization 3

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 The CSH2 (hCS-B) gene is expressed exclusively in placental tissue (not pituitary), as determined by screening pituitary and placental cDNA libraries with gene-specific oligonucleotides. The locus contains five genes with ~95% sequence identity; hCS-B is one of four placenta-specific members of the growth hormone gene cluster on chromosome 17. cDNA library screening with gene-specific oligonucleotides; full locus sequencing (~66,500 bp) Genomics High 2744760
1991 CSH2 (hCS-B) is expressed in placenta-derived choriocarcinoma BeWo cells (but not in JAR or JEG-3 cells, and not pituitary hGH-N), and treatment with 10 nM T3 causes a ~6-fold increase in CSH2 (and hCS-A and hGH-V) mRNA levels; cellular and secreted ~22 kDa protein is increased by T3 treatment as detected by Western blot. Oligonucleotide-specific Northern blotting of polyadenylated RNA; Western blotting of cellular and secreted protein; T3 treatment of BeWo cells Endocrinology Medium 1708334
1993 Treatment of BeWo choriocarcinoma cells with methotrexate (MTX) differentially suppresses CSH2 (hCS-B) and hCS-A relative to hGH-V; after MTX treatment only hGH-V and minor hCS-A transcripts were detected. MTX also blunts the T3-mediated increase in hCS/hGH-V transcripts without altering T3 receptor number or affinity, indicating MTX interferes with T3 responsiveness of the CSH2 gene. Northern blotting with gene-specific oligonucleotide probes; T3 receptor binding assay; MTX treatment of BeWo cells Molecular and cellular endocrinology Medium 8472847
1994 The transcriptional activity of the CSH2 (hCS-B) enhancer is mediated by two protein-binding sites, DF-3 and DF-4. Protein f (three polypeptides of ~12–21 kDa identified by UV cross-linking) binds the TEF-1-like motif within DF-4 and is important for placenta-specific activity of the hCS-B enhancer. Mutations in the TEF-1-like motif of DF-4 prevent complex f formation and greatly reduce transcriptional activity in JEG-3 cells. EMSA (electrophoretic mobility-shift assay); antibody supershift; UV cross-linking; transient expression with TKCAT constructs in JEG-3 cells DNA and cell biology Medium 7945936
1994 CSH2 (hCS-L is the pseudogene, not CSH2; this paper concerns hCS-L) — excluded as it is about the hCS-L pseudogene, not CSH2. N/A N/A Low 8083227
1995 The CSH2 (hCS-B) gene, along with hGH-N, requires a multicomponent locus control region (LCR) located ~15 and ~30 kb 5' of hGH-N for high-level, position-independent expression. DNase I hypersensitive sites (HS) common to both pituitary and placenta are required for placental gene expression; individually each set of HS loses physiologic control and tissue specificity, demonstrating synergistic interactions among multiple elements are needed for regulated expression of the hGH/hCS cluster including hCS-B. DNase I chromatin mapping; transgenic mouse integration of cosmid constructs; position-independence assay Molecular and cellular biology High 8524268
1996 The CSH2 (hCS-B) gene enhancer activity in syncytiotrophoblast primary culture is mediated by two elements, DF-3 and DF-4. A syncytiotrophoblast-specific protein binds the 3' part of DF-4, and targeted mutation of this site abolishes DF-4 element activity. The DF-3 element of hCS-B is more active than the homologous DF-3 in hCS-A due to a single naturally occurring base mutation that reduces activity in hCS-A. Replacement of the hCS-B DF-3 with the hCS-A sequence reduces hCS-B enhancer activity. During cytotrophoblast-to-syncytiotrophoblast differentiation in primary culture, hCS enhancers (including hCS-B) are progressively activated. Transient expression in primary syncytiotrophoblast culture; EMSA; targeted site-directed mutagenesis of enhancer elements DNA and cell biology Medium 8892756
1997 hTEF-5 (human TEF family transcription factor) is preferentially expressed in placenta and directly binds to multiple functional enhancer elements (TEF-binding sites) within the CSH2 (hCS-B) gene enhancer, as shown by EMSA and supershift assays. A tandemly repeated TEF-5 binding element in the hCS-B enhancer is bound cooperatively by hTEF-5. The corresponding hCS-A enhancer element is inactivated by a single naturally occurring base mutation that disrupts TEF-5 binding, explaining the differential activity of these two enhancers. EMSA; antibody supershift with anti-TEA domain monoclonal antibodies; site-directed mutagenesis; cDNA cloning and Northern blotting The Journal of biological chemistry High 9148898
1997 A 7 bp cAMP- and PMA-responsive element (CRElhCS-A) upstream of hCS-A mediates cAMP/phorbol ester responses, but the homologous sequence upstream of CSH2 (hCS-B), CRElhCS-B, differs by a single nucleotide substitution and shows little or no response to cAMP. Band-shift and Southwestern assays show CRElhCS-A binds a 100 kDa and a 47 kDa protein (related to CREBP and AP-1 respectively), while CRElhCS-B binds only the 47 kDa protein. The 100 kDa protein plays a crucial role in cAMP regulation specific to the hCS-A gene, while the 47 kDa protein is involved in PMA response of both hCS-A and hCS-B genes. Transient expression assays; EMSA (band-shift); Southwestern blotting Journal of molecular endocrinology Medium 9134496
2011 CCAAT/enhancer-binding protein (C/EBP) binding sites exist in the 80 bp modulatory domain of both the CSH2 (hCS-B) and hCS-A enhancers; an Elk-1 binding site is present in the CS-A enhancer modulatory domain. C/EBPα or C/EBPβ strongly represses CSH2 promoter activity alone but stimulates promoter activity when the hCS-B enhancer is present; the homologous CS-A enhancer sequences cannot relieve this repression. ChIP assays show differential association of C/EBPβ with CS-A and CS-B gene chromatin in human placenta, including differential involvement with their respective enhancers. EMSA; transient reporter assays in JEG-3 cells; chromatin immunoprecipitation (ChIP) in human placental chromatin Journal of molecular endocrinology High 21737519
2015 CSH2 mRNA displays an alternative splicing pattern in somatotroph pituitary adenomas. CSH2 isoform 3 is associated with a dense granulation pattern and an epithelial phenotype (high ESRP1 and E-cadherin expression) and is associated with reduced serum GH and IGF-I levels after somatostatin analog (SA) treatment, linking CSH2 splicing to treatment response. RNA sequencing (RNAseq); qRT-PCR in 65 somatotroph adenomas Neuro endocrinology letters Low 26071582
2015 Expression of placental CSH2 (hCS-B) and hCS-A genes in JEG-3 placental tumor cells is increased >10-fold by sequential treatment with the DNA methylation inhibitor 5-aza-2'-deoxycytidine (azadC) followed by the histone deacetylase inhibitor trichostatin A (TSA), but not by TSA alone or by reversing the treatment order. This is accompanied by increased histone H3/H4 acetylation at the hCS 3' enhancer sequences and LCR, indicating that DNA methylation restricts chromatin accessibility at these regulatory regions required for CSH2 expression. qRT-PCR of hCS-A, CS-B, GH-V RNA; ChIP for hyperacetylated H3/H4; luciferase reporter assays with hCS promoter constructs in JEG-3 and nonplacental cells BioResearch open access Medium 26634190
2018 Pre-pregnancy maternal obesity disrupts the placenta-specific chromosomal architecture at the hGH/CS locus, including interactions between upstream locus control region hypersensitive sites (HS III-V) and the CSH2 (hCS-B) and hCS-A gene promoters. In lean women, chromosome conformation capture detects preferential interactions between HS III-V and hCS (but not hGH) promoters; in obese women this architecture is disrupted and HS III preferentially interacts with the hGH-N promoter. Insulin treatment in obese women with gestational diabetes partially recapitulates the lean chromosomal architecture and positively affects hCS production. Decreased hCS levels in obesity are accompanied by reduced RNA polymerase II and C/EBPβ association with hCS promoter and enhancer sequences. Chromosome conformation capture (3C) assay; ChIP for RNA Pol II and C/EBPβ; quantitative PCR for hCS RNA levels American journal of physiology. Endocrinology and metabolism High 29763375
2018 Silencing CSH2 by RNAi in human sperm (in a model using hamster oocytes fertilized by HBV-transfected human sperm) causes a significant decrease in transcriptional levels of HBV s and x genes in the resulting embryo, indicating that CSH2 expression in sperm/embryo positively regulates HBV gene transcription. RNAi knockdown of CSH2 in human sperm; qRT-PCR of HBV s and x gene transcription in embryos derived from in vitro fertilization Asian journal of andrology Low 29111540
2014 CSH2 mRNA is detectable in breast cancer cell lines and some primary carcinomas; however, when CSH1/CSH2 mRNA was efficiently suppressed by shRNA, the immunoreactive 'hPL' band detected by certain commercial antibodies was not abolished, demonstrating those antibodies are non-specific. Custom monoclonal antibodies detected hPL protein only when mRNA was increased several thousand-fold, establishing that CSH2 mRNA is present in breast cancer but is not translated into protein under normal conditions. shRNA knockdown of CSH mRNA; Western blotting with multiple polyclonal and monoclonal antibodies (commercial and custom); immunohistochemistry; qRT-PCR PloS one Medium 24475273
2025 The PEG3/PW1 transcription factor binds to hypersensitive sites (HS III-V) within the hPL/CSH locus control region in CTB-like JEG-3 cells, and CSH2 (hPL-B) transcript levels increase upon PEG3 knockdown. In term placenta from obese women, PEG3 binding at placenta-specific HS IV is increased and hPL RNA levels are decreased; in obese women with insulin-treated gestational diabetes, PEG3 binding is reduced and hPL expression is increased. Chromosome conformation capture reveals distinct hPL gene domain interactions that are modified with obesity but largely reversed in O/GDM+Ins, correlating with PEG3 binding levels. ChIP for PEG3 at LCR hypersensitive sites; siRNA knockdown of PEG3 in JEG-3 cells; chromosome conformation capture (3C); qRT-PCR of hPL/CSH2 RNA levels in human placenta stratified by obesity/GDM status bioRxivpreprint Medium
2025 P sequences located upstream of all four placental hGH/PL genes (including CSH2/hPL-B) but not hGH-N repress hPL-A promoter activity in transfected pituitary GC cells and bind a forkhead box A1/nuclear factor-1 transcription factor complex proposed to act as a repressor in human pituitary chromatin. The LCR HS III interacts with P sequences in human pituitary chromatin as detected by chromosome conformation capture, suggesting a mechanism by which P sequences prevent CSH2 and other placental hGH/PL genes from being expressed in the pituitary. Transient transfection reporter assays in pituitary GC cells; EMSA for transcription factor binding to P sequences; chromosome conformation capture (3C) in human pituitary chromatin International journal of molecular sciences Medium 40362658
2016 In cultured bovine trophoblast cells, leptin supplementation increases CSH2 (chorionic somatomammotropin hormone 2/placental lactogen) transcript abundance at both 6 h and 24 h across all doses tested (10–250 ng/mL), while it does not affect interferon-tau (IFNT) expression or cell proliferation, indicating that leptin specifically upregulates CSH2 transcription in trophoblast cells. Graded recombinant bovine leptin treatment of cultured bovine trophoblast cells; qRT-PCR measurement of CSH2 and other transcripts; cell proliferation assay Domestic animal endocrinology Low 27743526

Source papers

Stage 0 corpus · 98 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity. American journal of human genetics 567 11992261
1989 The human growth hormone locus: nucleotide sequence, biology, and evolution. Genomics 425 2744760
2020 Molecular mechanism of SHP2 activation by PD-1 stimulation. Science advances 212 32064351
1995 Plasmid-mediated dissemination of the metallo-beta-lactamase gene blaIMP among clinically isolated strains of Serratia marcescens. Antimicrobial agents and chemotherapy 200 7785978
2011 Structure of lipid kinase p110β/p85β elucidates an unusual SH2-domain-mediated inhibitory mechanism. Molecular cell 167 21362552
1995 The human growth hormone gene is regulated by a multicomponent locus control region. Molecular and cellular biology 150 8524268
2020 Interaction of SHP-2 SH2 domains with PD-1 ITSM induces PD-1 dimerization and SHP-2 activation. Communications biology 146 32184441
2000 CAIR-1/BAG-3 forms an EGF-regulated ternary complex with phospholipase C-gamma and Hsp70/Hsc70. Oncogene 137 10980614
1996 Differential functions of the two Src homology 2 domains in protein tyrosine phosphatase SH-PTP1. Proceedings of the National Academy of Sciences of the United States of America 126 8577729
2017 Conformational disruption of PI3Kδ regulation by immunodeficiency mutations in PIK3CD and PIK3R1. Proceedings of the National Academy of Sciences of the United States of America 98 28167755
2013 Dissection of the BCR-ABL signaling network using highly specific monobody inhibitors to the SHP2 SH2 domains. Proceedings of the National Academy of Sciences of the United States of America 86 23980151
1993 Plasmid-mediated AmpC-type beta-lactamase isolated from Klebsiella pneumoniae confers resistance to broad-spectrum beta-lactams, including moxalactam. Antimicrobial agents and chemotherapy 83 8517725
2015 The Key Role of Calmodulin in KRAS-Driven Adenocarcinomas. Molecular cancer research : MCR 72 26085527
2016 A novel human autoimmune syndrome caused by combined hypomorphic and activating mutations in ZAP-70. The Journal of experimental medicine 71 26783323
2019 Gut Microbiota in Bipolar Depression and Its Relationship to Brain Function: An Advanced Exploration. Frontiers in psychiatry 63 31736803
1997 Human TEF-5 is preferentially expressed in placenta and binds to multiple functional elements of the human chorionic somatomammotropin-B gene enhancer. The Journal of biological chemistry 61 9148898
2014 Structure, function, and pathogenesis of SHP2 in developmental disorders and tumorigenesis. Current cancer drug targets 60 25039348
2011 Identification and characterization of a novel multipotent sub-population of Sca-1⁺ cardiac progenitor cells for myocardial regeneration. PloS one 56 21980409
2006 Sequence specificity of SHP-1 and SHP-2 Src homology 2 domains. Critical roles of residues beyond the pY+3 position. The Journal of biological chemistry 56 16702225
2017 Phosphorylated Calmodulin Promotes PI3K Activation by Binding to the SH2 Domains. Biophysical journal 54 29117520
1996 Interaction of the molecular weight 85K regulatory subunit of the phosphatidylinositol 3-kinase with the insulin receptor and the insulin-like growth factor-1 (IGF- I) receptor: comparative study using the yeast two-hybrid system. Endocrinology 51 8603569
1991 Tissue-specific expression and thyroid hormone regulation of the endogenous placental growth hormone variant and chorionic somatomammotropin genes in a human choriocarcinoma cell line. Endocrinology 43 1708334
2015 Two FGF Receptor Kinase Molecules Act in Concert to Recruit and Transphosphorylate Phospholipase Cγ. Molecular cell 42 26687682
2004 Novel mechanism of interaction of p85 subunit of phosphatidylinositol 3-kinase and ErbB3 receptor-derived phosphotyrosyl peptides. The Journal of biological chemistry 41 15520002
2021 Cryo-EM structures of PI3Kα reveal conformational changes during inhibition and activation. Proceedings of the National Academy of Sciences of the United States of America 36 34725156
1994 Complex alternative splicing partially inactivates the human chorionic somatomammotropin-like (hCS-L) gene. The Journal of biological chemistry 35 8083227
2019 Gain-of-Function SHP2 E76Q Mutant Rescuing Autoinhibition Mechanism Associated with Juvenile Myelomonocytic Leukemia. Journal of chemical information and modeling 33 31244092
2012 Activation of PI3K/Akt signaling by n-terminal SH2 domain mutants of the p85α regulatory subunit of PI3K is enhanced by deletion of its c-terminal SH2 domain. Cellular signalling 31 22735814
2011 Structural mechanism associated with domain opening in gain-of-function mutations in SHP2 phosphatase. Proteins 31 21365683
2014 The autoinhibitory C-terminal SH2 domain of phospholipase C-γ2 stabilizes B cell receptor signalosome assembly. Science signaling 29 25227611
2014 Extrapituitary growth hormone synthesis in humans. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society 26 24642386
2007 Structural and functional effects of disease-causing amino acid substitutions affecting residues Ala72 and Glu76 of the protein tyrosine phosphatase SHP-2. Proteins 26 17177198
2017 Domain analysis reveals striking functional differences between the regulatory subunits of phosphatidylinositol 3-kinase (PI3K), p85α and p85β. Oncotarget 25 28915558
2015 Oncogenic mutations of thyroid hormone receptor β. Oncotarget 25 25924236
1998 Physical and functional interaction between p72(syk) and erythropoietin receptor. The Journal of biological chemistry 24 9852052
2020 Structural Determinants of Phosphopeptide Binding to the N-Terminal Src Homology 2 Domain of the SHP2 Phosphatase. Journal of chemical information and modeling 23 32395997
2015 Assembly and Molecular Architecture of the Phosphoinositide 3-Kinase p85α Homodimer. The Journal of biological chemistry 22 26475863
2004 Genetics and variation in phenotype in Noonan syndrome. Hormone research 21 15539800
2021 Discriminating between competing models for the allosteric regulation of oncogenic phosphatase SHP2 by characterizing its active state. Computational and structural biotechnology journal 20 34900129
2018 Chromosomal architecture and placental expression of the human growth hormone gene family are targeted by pre-pregnancy maternal obesity. American journal of physiology. Endocrinology and metabolism 20 29763375
2018 Mechanism of Folding and Binding of the N-Terminal SH2 Domain from SHP2. The journal of physical chemistry. B 19 30047735
1996 The enhancers of the human placental lactogen B, A, and L genes: progressive activation during in vitro trophoblast differentiation and importance of the DF-3 element in determining their respective activities. DNA and cell biology 18 8892756
1994 A TEF-1 binding motif that interacts with a placental protein is important for the transcriptional activity of the hCS-B enhancer. DNA and cell biology 17 7945936
2018 Calmodulin (CaM) Activates PI3Kα by Targeting the "Soft" CaM-Binding Motifs in Both the nSH2 and cSH2 Domains of p85α. The journal of physical chemistry. B 16 30047727
2017 Calmodulin and IQGAP1 activation of PI3Kα and Akt in KRAS, HRAS and NRAS-driven cancers. Biochimica et biophysica acta. Molecular basis of disease 16 29097261
2007 Analysis of RNA species of various sizes from stationary-phase planktonic yeast cells of Candida albicans. FEMS yeast research 16 17311589
2023 Consideration of SHP-1 as a Molecular Target for Tumor Therapy. International journal of molecular sciences 15 38203502
2022 Nanobodies and chemical cross-links advance the structural and functional analysis of PI3Kα. Proceedings of the National Academy of Sciences of the United States of America 14 36095215
2022 mTORC1-GLUT1-mediated glucose metabolism drives hyperactivation of B cells in primary Sjogren's syndrome. Immunology 14 36155926
2021 Proteome profiling of human placenta reveals developmental stage-dependent alterations in protein signature. Clinical proteomics 14 34372761
1995 Regulation of protein tyrosine phosphatase 1C: opposing effects of the two src homology 2 domains. Protein engineering 14 8869644
2018 Transcription and regulation of hepatitis B virus genes in host sperm cells. Asian journal of andrology 13 29111540
2017 Characterization of clinically isolated thymidine-dependent small-colony variants of Escherichia coli producing extended-spectrum β-lactamase. Journal of medical microbiology 13 29143727
2024 Single-cell insights into development of the bovine placenta†. Biology of reproduction 12 37707543
2020 PIK3R1W624R Is an Actionable Mutation in High Grade Serous Ovarian Carcinoma. Cells 11 32075097
2020 LRRC4 Suppresses E-Cadherin-Dependent Collective Cell Invasion and Metastasis in Epithelial Ovarian Cancer. Frontiers in oncology 11 32117780
2019 Expression of growth hormone and growth hormone receptor genes in human eye tissues. Experimental eye research 11 30633923
2019 Design and evaluation of engineered protein biosensors for live-cell imaging of EGFR phosphorylation. Science signaling 10 31164479
2018 Interaction of Calmodulin with the cSH2 Domain of the p85 Regulatory Subunit. Biochemistry 10 29494137
2020 Molecular interactions of the CTLA-4 cytoplasmic region with the phosphoinositide 3-kinase SH2 domains. Molecular immunology 9 33386150
2018 Expression of growth hormone gene in the baboon eye. Experimental eye research 9 29407222
2018 Dynamic Allostery in PLCγ1 and Its Modulation by a Cancer Mutation Revealed by MD Simulation and NMR. Biophysical journal 9 29972810
2018 Exploring the effect of N308D mutation on protein tyrosine phosphatase-2 cause gain-of-function activity by a molecular dynamics study. Journal of cellular biochemistry 9 30304563
1993 Differential expression of human placental growth hormone variant and chorionic somatomammotropin genes in choriocarcinoma cells treated with methotrexate. Molecular and cellular endocrinology 9 8472847
2021 Determining folding and binding properties of the C-terminal SH2 domain of SHP2. Protein science : a publication of the Protein Society 8 34605082
2023 An intramolecular energetic network regulates ligand recognition in a SH2 domain. Protein science : a publication of the Protein Society 7 37468946
2005 PI3-kinase activation by GM-CSF in endothelium is upstream of Jak/Stat pathway: role of alphaGMR. Biochemical and biophysical research communications 7 16202975
2021 A novel likely pathogenic PLCG2 variant in a patient with a recurrent skin blistering disease and B-cell lymphopenia. European journal of medical genetics 6 34768012
2016 Activities for leptin in bovine trophoblast cells. Domestic animal endocrinology 6 27743526
2013 A new mutation in the C-SH2 domain of PTPN11 causes Noonan syndrome with multiple giant cell lesions. Journal of human genetics 6 24225993
2011 Identification of functional CCAAT/enhancer-binding protein and Ets protein binding sites in the human chorionic somatomammotropin enhancer sequences. Journal of molecular endocrinology 6 21737519
2023 Experiment-guided molecular simulations define a heterogeneous structural ensemble for the PTPN11 tandem SH2 domains. Chemical science 5 37265738
2023 Structural insights into the activation mechanism of phosphoinositide 3-kinase alpha. Computational biology and chemistry 5 38043374
2022 A kinetic model of phospholipase C-γ1 linking structure-based insights to dynamics of enzyme autoinhibition and activation. The Journal of biological chemistry 5 35367415
2021 Recruitment of phospholipase Cγ1 to the non-structural membrane protein pK15 of Kaposi Sarcoma-associated herpesvirus promotes its Src-dependent phosphorylation. PLoS pathogens 5 34143834
2021 The Conformational State of the BTK Substrate PLCγ Contributes to Ibrutinib Resistance. Journal of molecular biology 5 34954235
2017 Host genes regulate transcription of sperm-introduced hepatitis B virus genes in embryo. Reproductive toxicology (Elmsford, N.Y.) 5 28822827
2015 Alternative splicing of placental lactogen (CSH2) in somatotroph pituitary adenomas. Neuro endocrinology letters 5 26071582
2014 Placental lactogen is expressed but is not translated into protein in breast cancer. PloS one 5 24475273
2025 Gene signatures and genotype-phenotype correlations of sensorineural hearing loss in Noonan syndrome and related RASopathies. Scientific reports 4 40204880
2024 Folding and Binding Kinetics of the Tandem of SH2 Domains from SHP2. International journal of molecular sciences 4 38928272
2022 Characterization of early and late transition states of the folding pathway of a SH2 domain. Protein science : a publication of the Protein Society 4 35634781
2022 Regulation of CD28 binding to SH2 domains of Grb2 and PI3K by trisubstituted carboranes for T-cell activation. Bioorganic & medicinal chemistry letters 4 36356833
1986 [hGH and molecular biology]. Annales d'endocrinologie 4 3548571
2023 Structural characterization of the type I-B CRISPR Cas7 from Thermobaculum terrenum. Biochimica et biophysica acta. Proteins and proteomics 3 36682394
2020 1H, 13C, 15N chemical shift assignments of SHP2 SH2 domains in complex with PD-1 immune-tyrosine motifs. Biomolecular NMR assignments 3 32236803
2019 C-SH2 point mutation converts p85β regulatory subunit of phosphoinositide 3-kinase to an anti-aging gene. Scientific reports 3 31481652
2015 Expression of Placental Members of the Human Growth Hormone Gene Family Is Increased in Response to Sequential Inhibition of DNA Methylation and Histone Deacetylation. BioResearch open access 3 26634190
2025 Development of a Peptide Inhibitor Targeting the C-SH2 Domain of the SHP2 Phosphatase. Chembiochem : a European journal of chemical biology 2 40318117
2023 Mechanistic insights into the allosteric inactivation mechanism of ZAP-70 induced by the hot spot W165C mutation. Journal of biomolecular structure & dynamics 2 37505058
1997 A one-nucleotide difference in a cAMP and phorbol ester response element leads to differential regulation of the human chorionic somatomammotropin A and B gene transcription. Journal of molecular endocrinology 2 9134496
2025 Evidence for Pituitary Repression of the Human Growth Hormone-Related Placental Lactogen Genes and a Role for P Sequences. International journal of molecular sciences 1 40362658
2023 SHP-1 tyrosine phosphatase binding to c-Src kinase phosphor-dependent conformations: A comparative structural framework. PloS one 1 36638102
2023 Revealing Allostery in PTPN11 SH2 Domains from MD Simulations. Methods in molecular biology (Clifton, N.J.) 1 37668969
2026 Decoding C‑SH2 Domain/Peptide Interactions in SH2 Domain-Containing Tyrosine Phosphatase 2: A Molecular Framework for Rational Inhibitor Design. ACS omega 0 41658103
2026 Directed differentiation of bovine trophoblast stem cells: A useful in vitro model for placenta development. Proceedings of the National Academy of Sciences of the United States of America 0 41811437
2025 Cross-species identification of conserved cell-type specific mechanisms during early placenta development in ruminants. Scientific reports 0 41298965
2008 [SEREX screening of human placenta antigens]. Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 0 19253854

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