Deletion of the cytoplasmic domain increases basal shedding of angiotensin-converting enzyme

dc.contributor.authorChubb, Anthony J
dc.contributor.authorSchwager, Sylva L U
dc.contributor.authorvan der Merwe, Elizabeth
dc.contributor.authorEhlers, Mario R W
dc.contributor.authorSturrock, Edward D
dc.date.accessioned2016-09-01T08:09:03Z
dc.date.available2016-09-01T08:09:03Z
dc.date.issued2004
dc.date.updated2016-08-30T10:21:24Z
dc.description.abstractEctodomain shedding generates soluble isoforms of cell-surface proteins, including angiotensin-converting enzyme (ACE). Increasing evidence suggests that the juxtamembrane stalk of ACE, where proteolytic cleavage-release occurs, is not the major site of sheddase recognition. The role of the cytoplasmic domain has not been completely defined. We deleted the cytoplasmic domain of human testis ACE and found that this truncation mutant (ACE-ΔCYT) was shed constitutively from the surface of transfected CHO-K1 cells. Phorbol ester treatment produced only a slight increase in shedding of ACE-ΔCYT, unlike the marked stimulation seen with wild-type ACE. However, for both wild-type ACE and ACE-ΔCYT, shedding was inhibited by the peptide hydroxamate TAPI and the major cleavage site was identical, indicating the involvement of similar or identical sheddases. Cytochalasin D markedly increased the basal shedding of wild-type ACE but had little effect on the shedding of ACE-ΔCYT. These data suggest that the cytoplasmic domain of ACE interacts with the actin cytoskeleton and that this interaction is a negative regulator of ectodomain shedding.en_ZA
dc.identifierhttp://dx.doi.org/10.1016/j.bbrc.2003.12.198
dc.identifier.apacitationChubb, A. J., Schwager, S. L. U., van der Merwe, E., Ehlers, M. R. W., & Sturrock, E. D. (2004). Deletion of the cytoplasmic domain increases basal shedding of angiotensin-converting enzyme. <i>Biochemical and Biophysical Research Communications</i>, http://hdl.handle.net/11427/21636en_ZA
dc.identifier.chicagocitationChubb, Anthony J, Sylva L U Schwager, Elizabeth van der Merwe, Mario R W Ehlers, and Edward D Sturrock "Deletion of the cytoplasmic domain increases basal shedding of angiotensin-converting enzyme." <i>Biochemical and Biophysical Research Communications</i> (2004) http://hdl.handle.net/11427/21636en_ZA
dc.identifier.citationChubb, A. J., Schwager, S. L., van der Merwe, E., Ehlers, M. R., & Sturrock, E. D. (2004). Deletion of the cytoplasmic domain increases basal shedding of angiotensin-converting enzyme. Biochemical and biophysical research communications, 314(4), 971-975.en_ZA
dc.identifier.issn0006-291Xen_ZA
dc.identifier.ris TY - Journal Article AU - Chubb, Anthony J AU - Schwager, Sylva L U AU - van der Merwe, Elizabeth AU - Ehlers, Mario R W AU - Sturrock, Edward D AB - Ectodomain shedding generates soluble isoforms of cell-surface proteins, including angiotensin-converting enzyme (ACE). Increasing evidence suggests that the juxtamembrane stalk of ACE, where proteolytic cleavage-release occurs, is not the major site of sheddase recognition. The role of the cytoplasmic domain has not been completely defined. We deleted the cytoplasmic domain of human testis ACE and found that this truncation mutant (ACE-ΔCYT) was shed constitutively from the surface of transfected CHO-K1 cells. Phorbol ester treatment produced only a slight increase in shedding of ACE-ΔCYT, unlike the marked stimulation seen with wild-type ACE. However, for both wild-type ACE and ACE-ΔCYT, shedding was inhibited by the peptide hydroxamate TAPI and the major cleavage site was identical, indicating the involvement of similar or identical sheddases. Cytochalasin D markedly increased the basal shedding of wild-type ACE but had little effect on the shedding of ACE-ΔCYT. These data suggest that the cytoplasmic domain of ACE interacts with the actin cytoskeleton and that this interaction is a negative regulator of ectodomain shedding. DA - 2004 DB - OpenUCT DP - University of Cape Town J1 - Biochemical and Biophysical Research Communications LK - https://open.uct.ac.za PB - University of Cape Town PY - 2004 SM - 0006-291X T1 - Deletion of the cytoplasmic domain increases basal shedding of angiotensin-converting enzyme TI - Deletion of the cytoplasmic domain increases basal shedding of angiotensin-converting enzyme UR - http://hdl.handle.net/11427/21636 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/21636
dc.identifier.vancouvercitationChubb AJ, Schwager SLU, van der Merwe E, Ehlers MRW, Sturrock ED. Deletion of the cytoplasmic domain increases basal shedding of angiotensin-converting enzyme. Biochemical and Biophysical Research Communications. 2004; http://hdl.handle.net/11427/21636.en_ZA
dc.languageengen_ZA
dc.publisherElsevieren_ZA
dc.publisher.institutionUniversity of Cape Town
dc.sourceBiochemical and Biophysical Research Communicationsen_ZA
dc.source.urihttp://www.journals.elsevier.com/biochemical-and-biophysical-research-communications/
dc.subject.otherACE
dc.subject.otherEctodomain shedding
dc.subject.otherCytoplasmic domain
dc.subject.otherActin cytoskeleton
dc.subject.otherCytochalasin D
dc.titleDeletion of the cytoplasmic domain increases basal shedding of angiotensin-converting enzymeen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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