dc.contributor.author | Paterson, H | |
dc.date.accessioned | 2018-06-05T14:43:02Z | |
dc.date.issued | 2011-02 | |
dc.identifier | http://publications.icr.ac.uk/10425/ | |
dc.identifier.citation | CELLULAR SIGNALLING, 2011, 23 (2), pp. 468 - 477 | |
dc.identifier.issn | 0898-6568 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/1722 | |
dc.description.abstract | ERK1 and ERK2 (ERK1/2) are central to the regulation of cell division, growth and survival. They are activated by phosphorylation of the Thr- and the Tyr- residues in their Thr-Glu-Tyr activation loops. The dogma is that dually-phosphorylated ERK1/2 constitute the principal activities in intact cells. We previously showed that, in neonatal rat cardiac myocytes, endothelin-1 and phorbol 12-myristate 13-acetate (PMA) powerfully and rapidly (maximal at similar to 5 min) activate ERK1/2. Here, we show that dually-phosphorylated ERK1/2 rapidly (<2 min) appear in the nucleus following stimulation with endothelin-1. We characterized the active ERK1/2 species in myocytes exposed to endothelin-1 or PMA using MonoQ FPLC. Unexpectedly, two peaks of ERK1 and two peaks of ERK2 activity were resolved using in vitro kinase assays. One of each of these represented the dually-phosphorylated species. The other two represented activities for ERK1 or ERK2 which were phosphorylated solely on the Thr- residue. Monophosphothreonyl ERK1/2 represented maximally similar to 30% of total ERK1/2 activity after stimulation with endothelin-1 or PMA, and their k(cat) values were estimated to be minimally similar to 30% of the dually-phosphorylated species. Appearance of monophosphothreonyl ERK1/2 was rapid but delayed in comparison with dually-phosphorylated ERK1/2. Of 10 agonists studied, endothelin-1 and PMA were most effective in terms of ERK1/2 activation and in stimulating the appearance of monophosphothreonyl and dually-phosphorylated ERK1/2. Thus, enzymically active monophosphothreonyl ERK1/2 are formed endogenously following activation of the ERK1/2 cascade and we suggest that monophosphothreonyl ERK1/2 arise by protein tyrosine phosphatase-mediated dephosphorylation of dually-phosphorylated ERK1/2. (C) 2010 Elsevier Inc. All rights reserved. | |
dc.format.extent | 468 - 477 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | ELSEVIER SCIENCE INC | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | ERKs; Cardiac myocytes; Endothelin; Phorbol esters; Monophosphorylation;RAT VENTRICULAR MYOCYTES; PROTEIN-KINASE; DUAL PHOSPHORYLATION; CELLULAR STRESSES; GENE-EXPRESSION; IN-VIVO; C-JUN; ACTIVATION; STIMULATION; ERK2 | |
dc.title | Monophosphothreonyl extracellular signal-regulated kinases 1 and 2 (ERK1/2) are formed endogenously in intact cardiac myocytes and are enzymically active | |
dc.type | Journal Article | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2011-02 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | CELLULAR SIGNALLING | |
pubs.issue | 2 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams/Oncogene | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams/Oncogene | |
pubs.volume | 23 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Oncogene | en_US |
dc.contributor.icrauthor | Paterson, Hugh | en |