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Ribosomal RACK1:Protein Kinase C ßII Phosphorylates Eukaryotic Initiation Factor 4G1 at S1093 To Modulate Cap-Dependent and -Independent Translation Initiation.
Dobrikov, Mikhail I; Dobrikova, Elena Y; Gromeier, Matthias.
Afiliação
  • Dobrikov MI; Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina, USA.
  • Dobrikova EY; Departments of Molecular Genetics and of Microbiology and Neurosurgery, Duke University Medical Center, Durham, North Carolina, USA.
  • Gromeier M; Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina, USA.
Mol Cell Biol ; 38(19)2018 10 01.
Article em En | MEDLINE | ID: mdl-30012863
Eukaryotic ribosomes contain the high-affinity protein kinase C ßII (PKCßII) scaffold, receptor for activated C kinase (RACK1), but its role in protein synthesis control remains unclear. We found that RACK1:PKCßII phosphorylates eukaryotic initiation factor 4G1 (eIF4G1) at S1093 and eIF3a at S1364. We showed that reversible eIF4G(S1093) phosphorylation is involved in a global protein synthesis surge upon PKC-Raf-extracellular signal-regulated kinase 1/2 (ERK1/2) activation and in induction of phorbol ester-responsive transcripts, such as cyclooxygenase 2 (Cox-2) and cyclin-dependent kinase inhibitor (p21Cip1), or in 5' 7-methylguanosine (m7G) cap-independent enterovirus translation. Comparison of mRNA and protein levels revealed that eIF4G1 or RACK1 depletion blocked phorbol ester-induced Cox-2 or p21Cip1 expression mostly at the translational level, whereas PKCß inhibition reduced them both at the translational and transcript levels. Our findings reveal a physiological role for ribosomal RACK1 in providing the molecular scaffold for PKCßII and its role in coordinating the translational response to PKC-Raf-ERK1/2 activation.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fator de Iniciação Eucariótico 4G / Proteína Quinase C beta / Receptores de Quinase C Ativada / Proteínas de Neoplasias Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fator de Iniciação Eucariótico 4G / Proteína Quinase C beta / Receptores de Quinase C Ativada / Proteínas de Neoplasias Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article