Neuropeptides promote respiratory distress
Sci Signal. 2022 Apr 26;15(731):eabq6327. doi: 10.1126/scisignal.abq6327. Epub 2022 Apr 26.ABSTRACTIncreased neuropeptidergic signaling underlies lung dysfunction in a rare pediatric disease and may contribute to ARDS.PMID:35471942 | DOI:10.1126/scisignal.abq6327 (Source: Science Signaling)
Source: Science Signaling - April 26, 2022 Category: Biomedical Science Authors: Annalisa M VanHook Source Type: research

Structural analysis of TrkA mutations in patients with congenital insensitivity to pain reveals PLC γ as an analgesic drug target
Sci Signal. 2022 Apr 26;15(731):eabm6046. doi: 10.1126/scisignal.abm6046. Epub 2022 Apr 26.ABSTRACTChronic pain is a major health issue, and the search for new analgesics has become increasingly important because of the addictive properties and unwanted side effects of opioids. To explore potentially new drug targets, we investigated mutations in the NTRK1 gene found in individuals with congenital insensitivity to pain with anhidrosis (CIPA). NTRK1 encodes tropomyosin receptor kinase A (TrkA), the receptor for nerve growth factor (NGF) and that contributes to nociception. Molecular modeling and biochemical analysis identif...
Source: Science Signaling - April 26, 2022 Category: Biomedical Science Authors: Beatriz C Moraes Helder V Ribeiro-Filho Allan P Rold ão Elaine F Toniolo Gustavo P B Carretero Germ án G Sgro Fernanda A H Batista Damian E Berardi Victoria R S Oliveira Rebeka Tomasin Felipe M Vieceli Dimitrius T Pramio Alexandre B Cardoso Ana C M Figu Source Type: research

Targeting the lysine-specific demethylase 1 rewires kinase networks and primes leukemia cells for kinase inhibitor treatment
Sci Signal. 2022 Apr 19;15(730):eabl7989. doi: 10.1126/scisignal.abl7989. Epub 2022 Apr 19.ABSTRACTMost tumor types either fail to respond or become resistant to kinase inhibitors, often because of compensatory prosurvival pathways in the cancer cell's broader signaling circuitry. Here, we found that intrinsic resistance to kinase inhibitors in cultured primary acute myeloid leukemia (AML) cells may be overcome by reshaping kinase networks into topologies that confer drug sensitivity. We identified several antagonists of chromatin-modifying enzymes that sensitized AML cell lines to kinase inhibitors. Of these, we confirmed...
Source: Science Signaling - April 19, 2022 Category: Biomedical Science Authors: Federico Pedicona Pedro Casado Maruan Hijazi John G Gribben Kevin Rouault-Pierre Pedro R Cutillas Source Type: research

Targeting AML at the intersection of epigenetics and signaling
Sci Signal. 2022 Apr 19;15(730):eabo0059. doi: 10.1126/scisignal.abo0059. Epub 2022 Apr 19.ABSTRACTMutations in multiple cancers may synergize to alter the cellular epigenetic and transcriptional state and corrupt key signaling pathways. In this issue of Science Signaling, Pedicona et al. illustrate how the two processes intersect to regulate cellular differentiation in acute myeloid leukemia (AML) and show how inhibition of epigenetic regulators promotes sensitivity to kinase inhibitors.PMID:35439022 | DOI:10.1126/scisignal.abo0059 (Source: Science Signaling)
Source: Science Signaling - April 19, 2022 Category: Biomedical Science Authors: Nisha Narayan Brian J P Huntly Source Type: research

Protein tyrosine phosphatase 1B regulates miR-208b-argonaute 2 association and thyroid hormone responsiveness in cardiac hypertrophy
Sci Signal. 2022 Apr 19;15(730):eabn6875. doi: 10.1126/scisignal.abn6875. Epub 2022 Apr 19.ABSTRACTIncreased production of reactive oxygen species plays an essential role in the pathogenesis of several diseases, including cardiac hypertrophy. In our search to identify redox-sensitive targets that contribute to redox signaling, we found that protein tyrosine phosphatase 1B (PTP1B) was reversibly oxidized and inactivated in hearts undergoing hypertrophy. Cardiomyocyte-specific deletion of PTP1B in mice (PTP1B cKO mice) caused a hypertrophic phenotype that was exacerbated by pressure overload. Furthermore, we showed that argo...
Source: Science Signaling - April 19, 2022 Category: Biomedical Science Authors: G érald Coulis Avinash D Londhe R Sudheer Sagabala Yanfen Shi David P Labb é Alexandre Bergeron Pramod Sahadevan Sherin A Nawaito Fatiha Sahmi Marie Josse Val érie Vinette Marie-Claude Guertin G érard Karsenty Michel L Tremblay Jean-Claude Tardif Bruc Source Type: research

Shining a light on rhodopsin signaling
Sci Signal. 2022 Apr 19;15(730):eabq5583. doi: 10.1126/scisignal.abq5583. Epub 2022 Apr 19.ABSTRACTMonitoring rhodopsin signaling in real time reveals the role of native lipids in modulating GPCR interactions.PMID:35439024 | DOI:10.1126/scisignal.abq5583 (Source: Science Signaling)
Source: Science Signaling - April 19, 2022 Category: Biomedical Science Authors: John F Foley Source Type: research

Targeting the lysine-specific demethylase 1 rewires kinase networks and primes leukemia cells for kinase inhibitor treatment
Sci Signal. 2022 Apr 19;15(730):eabl7989. doi: 10.1126/scisignal.abl7989. Epub 2022 Apr 19.ABSTRACTMost tumor types either fail to respond or become resistant to kinase inhibitors, often because of compensatory prosurvival pathways in the cancer cell's broader signaling circuitry. Here, we found that intrinsic resistance to kinase inhibitors in cultured primary acute myeloid leukemia (AML) cells may be overcome by reshaping kinase networks into topologies that confer drug sensitivity. We identified several antagonists of chromatin-modifying enzymes that sensitized AML cell lines to kinase inhibitors. Of these, we confirmed...
Source: Science Signaling - April 19, 2022 Category: Biomedical Science Authors: Federico Pedicona Pedro Casado Maruan Hijazi John G Gribben Kevin Rouault-Pierre Pedro R Cutillas Source Type: research

Targeting AML at the intersection of epigenetics and signaling
Sci Signal. 2022 Apr 19;15(730):eabo0059. doi: 10.1126/scisignal.abo0059. Epub 2022 Apr 19.ABSTRACTMutations in multiple cancers may synergize to alter the cellular epigenetic and transcriptional state and corrupt key signaling pathways. In this issue of Science Signaling, Pedicona et al. illustrate how the two processes intersect to regulate cellular differentiation in acute myeloid leukemia (AML) and show how inhibition of epigenetic regulators promotes sensitivity to kinase inhibitors.PMID:35439022 | DOI:10.1126/scisignal.abo0059 (Source: Science Signaling)
Source: Science Signaling - April 19, 2022 Category: Biomedical Science Authors: Nisha Narayan Brian J P Huntly Source Type: research

Protein tyrosine phosphatase 1B regulates miR-208b-argonaute 2 association and thyroid hormone responsiveness in cardiac hypertrophy
Sci Signal. 2022 Apr 19;15(730):eabn6875. doi: 10.1126/scisignal.abn6875. Epub 2022 Apr 19.ABSTRACTIncreased production of reactive oxygen species plays an essential role in the pathogenesis of several diseases, including cardiac hypertrophy. In our search to identify redox-sensitive targets that contribute to redox signaling, we found that protein tyrosine phosphatase 1B (PTP1B) was reversibly oxidized and inactivated in hearts undergoing hypertrophy. Cardiomyocyte-specific deletion of PTP1B in mice (PTP1B cKO mice) caused a hypertrophic phenotype that was exacerbated by pressure overload. Furthermore, we showed that argo...
Source: Science Signaling - April 19, 2022 Category: Biomedical Science Authors: G érald Coulis Avinash D Londhe R Sudheer Sagabala Yanfen Shi David P Labb é Alexandre Bergeron Pramod Sahadevan Sherin A Nawaito Fatiha Sahmi Marie Josse Val érie Vinette Marie-Claude Guertin G érard Karsenty Michel L Tremblay Jean-Claude Tardif Bruc Source Type: research

Shining a light on rhodopsin signaling
Sci Signal. 2022 Apr 19;15(730):eabq5583. doi: 10.1126/scisignal.abq5583. Epub 2022 Apr 19.ABSTRACTMonitoring rhodopsin signaling in real time reveals the role of native lipids in modulating GPCR interactions.PMID:35439024 | DOI:10.1126/scisignal.abq5583 (Source: Science Signaling)
Source: Science Signaling - April 19, 2022 Category: Biomedical Science Authors: John F Foley Source Type: research

Targeting the lysine-specific demethylase 1 rewires kinase networks and primes leukemia cells for kinase inhibitor treatment
Sci Signal. 2022 Apr 19;15(730):eabl7989. doi: 10.1126/scisignal.abl7989. Epub 2022 Apr 19.ABSTRACTMost tumor types either fail to respond or become resistant to kinase inhibitors, often because of compensatory prosurvival pathways in the cancer cell's broader signaling circuitry. Here, we found that intrinsic resistance to kinase inhibitors in cultured primary acute myeloid leukemia (AML) cells may be overcome by reshaping kinase networks into topologies that confer drug sensitivity. We identified several antagonists of chromatin-modifying enzymes that sensitized AML cell lines to kinase inhibitors. Of these, we confirmed...
Source: Science Signaling - April 19, 2022 Category: Biomedical Science Authors: Federico Pedicona Pedro Casado Maruan Hijazi John G Gribben Kevin Rouault-Pierre Pedro R Cutillas Source Type: research

Targeting AML at the intersection of epigenetics and signaling
Sci Signal. 2022 Apr 19;15(730):eabo0059. doi: 10.1126/scisignal.abo0059. Epub 2022 Apr 19.ABSTRACTMutations in multiple cancers may synergize to alter the cellular epigenetic and transcriptional state and corrupt key signaling pathways. In this issue of Science Signaling, Pedicona et al. illustrate how the two processes intersect to regulate cellular differentiation in acute myeloid leukemia (AML) and show how inhibition of epigenetic regulators promotes sensitivity to kinase inhibitors.PMID:35439022 | DOI:10.1126/scisignal.abo0059 (Source: Science Signaling)
Source: Science Signaling - April 19, 2022 Category: Biomedical Science Authors: Nisha Narayan Brian J P Huntly Source Type: research

Protein tyrosine phosphatase 1B regulates miR-208b-argonaute 2 association and thyroid hormone responsiveness in cardiac hypertrophy
Sci Signal. 2022 Apr 19;15(730):eabn6875. doi: 10.1126/scisignal.abn6875. Epub 2022 Apr 19.ABSTRACTIncreased production of reactive oxygen species plays an essential role in the pathogenesis of several diseases, including cardiac hypertrophy. In our search to identify redox-sensitive targets that contribute to redox signaling, we found that protein tyrosine phosphatase 1B (PTP1B) was reversibly oxidized and inactivated in hearts undergoing hypertrophy. Cardiomyocyte-specific deletion of PTP1B in mice (PTP1B cKO mice) caused a hypertrophic phenotype that was exacerbated by pressure overload. Furthermore, we showed that argo...
Source: Science Signaling - April 19, 2022 Category: Biomedical Science Authors: G érald Coulis Avinash D Londhe R Sudheer Sagabala Yanfen Shi David P Labb é Alexandre Bergeron Pramod Sahadevan Sherin A Nawaito Fatiha Sahmi Marie Josse Val érie Vinette Marie-Claude Guertin G érard Karsenty Michel L Tremblay Jean-Claude Tardif Bruc Source Type: research

Shining a light on rhodopsin signaling
Sci Signal. 2022 Apr 19;15(730):eabq5583. doi: 10.1126/scisignal.abq5583. Epub 2022 Apr 19.ABSTRACTMonitoring rhodopsin signaling in real time reveals the role of native lipids in modulating GPCR interactions.PMID:35439024 | DOI:10.1126/scisignal.abq5583 (Source: Science Signaling)
Source: Science Signaling - April 19, 2022 Category: Biomedical Science Authors: John F Foley Source Type: research

Targeting the lysine-specific demethylase 1 rewires kinase networks and primes leukemia cells for kinase inhibitor treatment
Sci Signal. 2022 Apr 19;15(730):eabl7989. doi: 10.1126/scisignal.abl7989. Epub 2022 Apr 19.ABSTRACTMost tumor types either fail to respond or become resistant to kinase inhibitors, often because of compensatory prosurvival pathways in the cancer cell's broader signaling circuitry. Here, we found that intrinsic resistance to kinase inhibitors in cultured primary acute myeloid leukemia (AML) cells may be overcome by reshaping kinase networks into topologies that confer drug sensitivity. We identified several antagonists of chromatin-modifying enzymes that sensitized AML cell lines to kinase inhibitors. Of these, we confirmed...
Source: Science Signaling - April 19, 2022 Category: Biomedical Science Authors: Federico Pedicona Pedro Casado Maruan Hijazi John G Gribben Kevin Rouault-Pierre Pedro R Cutillas Source Type: research