ArticleMolecular endocrinology (Baltimore, Md.)2007
Proline-rich tyrosine kinase 2 mediates gonadotropin-releasing hormone signaling to a specific extracellularly regulated kinase-sensitive transcriptional locus in the luteinizing hormone beta-subunit gene.
Article in Molecular endocrinology (Baltimore, Md.), 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 40 citations in OpenAlex.
- The effects of aging on the BTBR mouse model of autism spectrum disorder.Frontiers in aging neuroscience · 2014Article
- BRET Biosensor Analysis of Receptor Tyrosine Kinase Functionality.Frontiers in endocrinology · 2013Article
- Functional signaling biases in G protein-coupled receptors: Game Theory and receptor dynamics.Mini reviews in medicinal chemistry · 2012Review
- GnRH regulation of Jun and Atf3 requires calcium, calcineurin, and NFAT.Molecular endocrinology (Baltimore, Md.) · 2012Article
- Characterization of a MAPK scaffolding protein logic gate in gonadotropes.Molecular endocrinology (Baltimore, Md.) · 2011Article
- PPARG regulates gonadotropin-releasing hormone signaling in LbetaT2 cells in vitro and pituitary gonadotroph function in vivo in mice.Biology of reproduction · 2011Article
- Repetitive peroxide exposure reveals pleiotropic mitogen-activated protein kinase signaling mechanisms.Journal of signal transduction · 2011Article
- Gonadotropin-releasing hormone receptor system: modulatory role in aging and neurodegeneration.CNS & neurological disorders drug targets · 2010Review
- Modulation of gonadotropin-releasing hormone-induced extracellular signal-regulated kinase activation by dual-specificity protein phosphatase 1 in LbetaT2 gonadotropes.Endocrinology · 2010Article
- GnRH signaling, the gonadotrope and endocrine control of fertility.Frontiers in neuroendocrinology · 2010Review
- Regulation of Lhb and Egr1 gene expression by GNRH pulses in rat pituitaries is both c-Jun N-terminal kinase (JNK)- and extracellular signal-regulated kinase (ERK)-dependent.Biology of reproduction · 2009Article
- Insulin augments gonadotropin-releasing hormone induction of translation in LbetaT2 cells.Molecular and cellular endocrinology · 2009Article
- A preformed signaling complex mediates GnRH-activated ERK phosphorylation of paxillin and FAK at focal adhesions in L beta T2 gonadotrope cells.Molecular endocrinology (Baltimore, Md.) · 2009Article
- ERK signaling in the pituitary is required for female but not male fertility.Molecular endocrinology (Baltimore, Md.) · 2009Article
- Conservation of mechanisms mediating gonadotrophin-releasing hormone 1 stimulation of human luteinizing hormone beta subunit transcription.Molecular human reproduction · 2009Article
- Growth factor signals in neural cells: coherent patterns of interaction control multiple levels of molecular and phenotypic responses.The Journal of biological chemistry · 2009Article
- Analysis of the calcium-dependent regulation of proline-rich tyrosine kinase 2 by gonadotropin-releasing hormone.Molecular endocrinology (Baltimore, Md.) · 2008Article
- Caloric restriction: impact upon pituitary function and reproduction.Ageing research reviews · 2008Review
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
G protein-coupled receptor regulation of gene transcription primarily occurs through the phosphorylation of transcription factors by MAPKs. This requires transduction of an activating signal via scaffold proteins that can ultimately determine the outcome by binding signaling kinases and adapter proteins with effects on the target transcription factor and locus of activation. By investigating these mechanisms, we have elucidated how pituitary gonadotrope cells decode an input GnRH signal into coherent transcriptional output from the LH beta-subunit gene promoter. We show that GnRH activates c-Src and multiple members of the MAPK family, c-Jun NH2-terminal kinase 1/2, p38MAPK, and ERK1/2. Using dominant-negative point mutations and chemical inhibitors, we identified that calcium-dependent proline-rich tyrosine kinase 2 specifically acts as a scaffold for a focal adhesion/cytoskeleton-dependent complex comprised of c-Src, Grb2, and mSos that translocates an ERK-activating signal to the nucleus. The locus of action of ERK was specifically mapped to early growth response-1 (Egr-1) DNA binding sites within the LH beta-subunit gene proximal promoter, which was also activated by p38MAPK, but not c-Jun NH2-terminal kinase 1/2. Egr-1 was confirmed as the transcription factor target of ERK and p38MAPK by blockade of protein expression, transcriptional activity, and DNA binding. We have identified a novel GnRH-activated proline-rich tyrosine kinase 2-dependent ERK-mediated signal transduction pathway that specifically regulates Egr-1 activation of the LH beta-subunit proximal gene promoter, and thus provide insight into the molecular mechanisms required for differential regulation of gonadotropin gene expression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.