FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2015137255> ?p ?o ?g. }

• W2015137255 endingPage "15034" @default.
• W2015137255 startingPage "15023" @default.
• W2015137255 abstract "The corticotropin-releasing factor (CRF) receptor 1 (CRFR1) is a target for the treatment of psychiatric diseases such as depression, schizophrenia, anxiety disorder, and bipolar disorder. The carboxyl-terminal tail of the CRFR1 terminates in a PDZ-binding motif that provides a potential site for the interaction of PSD-95/Discs Large/Zona Occludens 1 (PDZ) domain-containing proteins. In this study, we found that CRFR1 interacts with synapse-associated protein 97 (SAP97; also known as DLG1) by co-immunoprecipitation in human embryonic 293 (HEK 293) cells and cortical brain lysates and that this interaction is dependent upon an intact PDZ-binding motif at the end of the CRFR1 carboxyl-terminal tail. Similarly, we demonstrated that SAP97 is recruited to the plasma membrane in HEK 293 cells expressing CRFR1 and that mutation of the CRFR1 PDZ-binding motif results in the redistribution of SAP97 into the cytoplasm. Overexpression of SAP97 antagonized agonist-stimulated CRFR1 internalization, whereas single hairpin (shRNA) knockdown of endogenous SAP97 in HEK 293 cells resulted in increased agonist-stimulated CRFR1 endocytosis. CRFR1 was internalized as a complex with SAP97 resulting in the redistribution of SAP97 to endocytic vesicles. Overexpression or shRNA knockdown of SAP97 did not significantly affect CRFR1-mediated cAMP formation, but SAP97 knockdown did significantly attenuate CRFR1-stimulated ERK1/2 phosphorylation in a PDZ interaction-independent manner. Taken together, our studies show that SAP97 interactions with CRFR1 attenuate CRFR1 endocytosis and that SAP97 is involved in coupling G protein-coupled receptors to the activation of the ERK1/2 signaling pathway.Background: CRFR1 regulates the physiological response to stress and is implicated in the manifestation of depression.Results: SAP97 interacts and co-localizes with CRFR1, suppresses CRFR1 endocytosis, and is required for CRFR1-mediated ERK1/2 phosphorylation.Conclusion: SAP97 functionally regulates CRFR1 trafficking and signaling.Significance: This is the first documentation of functional regulation of CRFR1 by a specific PDZ protein. The corticotropin-releasing factor (CRF) receptor 1 (CRFR1) is a target for the treatment of psychiatric diseases such as depression, schizophrenia, anxiety disorder, and bipolar disorder. The carboxyl-terminal tail of the CRFR1 terminates in a PDZ-binding motif that provides a potential site for the interaction of PSD-95/Discs Large/Zona Occludens 1 (PDZ) domain-containing proteins. In this study, we found that CRFR1 interacts with synapse-associated protein 97 (SAP97; also known as DLG1) by co-immunoprecipitation in human embryonic 293 (HEK 293) cells and cortical brain lysates and that this interaction is dependent upon an intact PDZ-binding motif at the end of the CRFR1 carboxyl-terminal tail. Similarly, we demonstrated that SAP97 is recruited to the plasma membrane in HEK 293 cells expressing CRFR1 and that mutation of the CRFR1 PDZ-binding motif results in the redistribution of SAP97 into the cytoplasm. Overexpression of SAP97 antagonized agonist-stimulated CRFR1 internalization, whereas single hairpin (shRNA) knockdown of endogenous SAP97 in HEK 293 cells resulted in increased agonist-stimulated CRFR1 endocytosis. CRFR1 was internalized as a complex with SAP97 resulting in the redistribution of SAP97 to endocytic vesicles. Overexpression or shRNA knockdown of SAP97 did not significantly affect CRFR1-mediated cAMP formation, but SAP97 knockdown did significantly attenuate CRFR1-stimulated ERK1/2 phosphorylation in a PDZ interaction-independent manner. Taken together, our studies show that SAP97 interactions with CRFR1 attenuate CRFR1 endocytosis and that SAP97 is involved in coupling G protein-coupled receptors to the activation of the ERK1/2 signaling pathway. Background: CRFR1 regulates the physiological response to stress and is implicated in the manifestation of depression. Results: SAP97 interacts and co-localizes with CRFR1, suppresses CRFR1 endocytosis, and is required for CRFR1-mediated ERK1/2 phosphorylation. Conclusion: SAP97 functionally regulates CRFR1 trafficking and signaling. Significance: This is the first documentation of functional regulation of CRFR1 by a specific PDZ protein." @default.
• W2015137255 created "2016-06-24" @default.
• W2015137255 creator A5001319749 @default.
• W2015137255 creator A5002184611 @default.
• W2015137255 creator A5055889724 @default.
• W2015137255 creator A5078112449 @default.
• W2015137255 creator A5081172086 @default.
• W2015137255 date "2013-05-01" @default.
• W2015137255 modified "2023-09-30" @default.
• W2015137255 title "Role of SAP97 Protein in the Regulation of Corticotropin-releasing Factor Receptor 1 Endocytosis and Extracellular Signal-regulated Kinase 1/2 Signaling" @default.
• W2015137255 cites W1951492130 @default.
• W2015137255 cites W1976016445 @default.
• W2015137255 cites W1979199686 @default.
• W2015137255 cites W1981568254 @default.
• W2015137255 cites W1986000840 @default.
• W2015137255 cites W1988594478 @default.
• W2015137255 cites W2000272692 @default.
• W2015137255 cites W2007352125 @default.
• W2015137255 cites W2007843119 @default.
• W2015137255 cites W2008186223 @default.
• W2015137255 cites W2018146224 @default.
• W2015137255 cites W2020421701 @default.
• W2015137255 cites W2026868761 @default.
• W2015137255 cites W2027082069 @default.
• W2015137255 cites W2041981656 @default.
• W2015137255 cites W2046013541 @default.
• W2015137255 cites W2048358065 @default.
• W2015137255 cites W2049674122 @default.
• W2015137255 cites W2058995181 @default.
• W2015137255 cites W2059692874 @default.
• W2015137255 cites W2061983836 @default.
• W2015137255 cites W2064264742 @default.
• W2015137255 cites W2071736830 @default.
• W2015137255 cites W2073458421 @default.
• W2015137255 cites W2079523532 @default.
• W2015137255 cites W2079882316 @default.
• W2015137255 cites W2081148376 @default.
• W2015137255 cites W2081294643 @default.
• W2015137255 cites W2082827602 @default.
• W2015137255 cites W2090623858 @default.
• W2015137255 cites W2095036452 @default.
• W2015137255 cites W2096227949 @default.
• W2015137255 cites W2098001295 @default.
• W2015137255 cites W2115940067 @default.
• W2015137255 cites W2116265895 @default.
• W2015137255 cites W2116354283 @default.
• W2015137255 cites W2129763785 @default.
• W2015137255 cites W2132740087 @default.
• W2015137255 cites W2132797631 @default.
• W2015137255 cites W2133167066 @default.
• W2015137255 cites W2137273425 @default.
• W2015137255 cites W2143463649 @default.
• W2015137255 cites W2143594596 @default.
• W2015137255 cites W2143891666 @default.
• W2015137255 cites W2149757555 @default.
• W2015137255 cites W2154597715 @default.
• W2015137255 cites W2155626008 @default.
• W2015137255 cites W2159970885 @default.
• W2015137255 cites W2164606563 @default.
• W2015137255 cites W2167549203 @default.
• W2015137255 cites W2170177649 @default.
• W2015137255 cites W4376848280 @default.
• W2015137255 doi "https://doi.org/10.1074/jbc.m113.473660" @default.
• W2015137255 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3663523" @default.
• W2015137255 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23576434" @default.
• W2015137255 hasPublicationYear "2013" @default.
• W2015137255 type Work @default.
• W2015137255 sameAs 2015137255 @default.
• W2015137255 citedByCount "29" @default.
• W2015137255 countsByYear W20151372552014 @default.
• W2015137255 countsByYear W20151372552015 @default.
• W2015137255 countsByYear W20151372552016 @default.
• W2015137255 countsByYear W20151372552017 @default.
• W2015137255 countsByYear W20151372552018 @default.
• W2015137255 countsByYear W20151372552019 @default.
• W2015137255 countsByYear W20151372552021 @default.
• W2015137255 countsByYear W20151372552023 @default.
• W2015137255 crossrefType "journal-article" @default.
• W2015137255 hasAuthorship W2015137255A5001319749 @default.
• W2015137255 hasAuthorship W2015137255A5002184611 @default.
• W2015137255 hasAuthorship W2015137255A5055889724 @default.
• W2015137255 hasAuthorship W2015137255A5078112449 @default.
• W2015137255 hasAuthorship W2015137255A5081172086 @default.
• W2015137255 hasBestOaLocation W20151372551 @default.
• W2015137255 hasConcept C12554922 @default.
• W2015137255 hasConcept C139770010 @default.
• W2015137255 hasConcept C154428179 @default.
• W2015137255 hasConcept C170493617 @default.
• W2015137255 hasConcept C173396325 @default.
• W2015137255 hasConcept C174510640 @default.
• W2015137255 hasConcept C190232843 @default.
• W2015137255 hasConcept C26659971 @default.
• W2015137255 hasConcept C28005876 @default.
• W2015137255 hasConcept C41625074 @default.
• W2015137255 hasConcept C53645450 @default.
• W2015137255 hasConcept C54355233 @default.
• W2015137255 hasConcept C55493867 @default.
• W2015137255 hasConcept C62478195 @default.

• next