{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lange S"],"funding":["British Heart Foundation","Telethon","NHLBI NIH HHS","Medical Research Council","NINDS NIH HHS"],"pagination":["12120"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4931343"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["7"],"pubmed_abstract":["MLP (muscle LIM protein)-deficient mice count among the first mouse models for dilated cardiomyopathy (DCM), yet the exact role of MLP in cardiac signalling processes is still enigmatic. Elevated PKCα signalling activity is known to be an important contributor to heart failure. Here we show that MLP directly inhibits the activity of PKCα. In end-stage DCM, PKCα is concentrated at the intercalated disc of cardiomyocytes, where it is sequestered by the adaptor protein CARP in a multiprotein complex together with PLCβ1. In mice deficient for both MLP and CARP the chronic PKCα signalling chain at the intercalated disc is broken and they remain healthy. Our results suggest that the main role of MLP in heart lies in the direct inhibition of PKCα and that chronic uninhibited PKCα activity at the intercalated disc in the absence of functional MLP leads to heart failure."],"journal":["Nature communications"],"pubmed_title":["MLP and CARP are linked to chronic PKCα signalling in dilated cardiomyopathy."],"pmcid":["PMC4931343"],"funding_grant_id":["R01 HL123626","GGP12282","R01 HL130452","P30 NS047101","K99 HL107744","G0400153","R00 HL107744","R01 HL130295","FS/12/40/29712","R01 HL106968","R01 HL128457","R01 HL066100"],"pubmed_authors":["Chen J","Peterson KL","Blondelle J","Abassi YA","Alvarez EA","Gehmlich K","Dalton ND","Lange S","Hooper C","Zhang X","Bang ML","Ehler E","Dos Remedios CG","Lun AS"],"additional_accession":[]},"is_claimable":false,"name":"MLP and CARP are linked to chronic PKCα signalling in dilated cardiomyopathy.","description":"MLP (muscle LIM protein)-deficient mice count among the first mouse models for dilated cardiomyopathy (DCM), yet the exact role of MLP in cardiac signalling processes is still enigmatic. Elevated PKCα signalling activity is known to be an important contributor to heart failure. Here we show that MLP directly inhibits the activity of PKCα. In end-stage DCM, PKCα is concentrated at the intercalated disc of cardiomyocytes, where it is sequestered by the adaptor protein CARP in a multiprotein complex together with PLCβ1. In mice deficient for both MLP and CARP the chronic PKCα signalling chain at the intercalated disc is broken and they remain healthy. Our results suggest that the main role of MLP in heart lies in the direct inhibition of PKCα and that chronic uninhibited PKCα activity at the intercalated disc in the absence of functional MLP leads to heart failure.","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Jun","modification":"2025-04-26T22:06:22.381Z","creation":"2019-03-27T02:17:28Z"},"accession":"S-EPMC4931343","cross_references":{"pubmed":["27353086"],"doi":["10.1038/ncomms12120"]}}