c-Cbl is not required for ERK1/2-dependent degradation of BimEL

Ceri M. Wiggins, Hamid Band, Simon J. Cook

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

BimEL the most abundant Bim splice variant, is subject to ERK1/2-catalysed phosphorylation, which targets it for ubiquitination and proteasome-dependent destruction. In contrast, inactivation of ERK1/2, following withdrawal of survival factors, promotes stabilization of BimEL. It has been proposed that the RING finger protein Cbl binds to BimEL and serves as its E3 ubiquitin ligase. However, this is controversial since most Cbl substrates are tyrosine phosphoproteins and yet BimEL is targeted for destruction by ERK1/2-catalysed serine phosphorylation. Consequently, a role for Cbl could suggest a second pathway for BimEL turnover, regulated by direct tyrosine phosphorylation, or could suggest that BimEL is a coincidence detector, requiring phosphorylation by ERK1/2 and a tyrosine kinase. Here we show that degradation of BimEL does not involve its tyrosine phosphorylation; indeed, BimEL is not a tyrosine phosphoprotein. Furthermore, BimEL fails to interact with Cbl and growth factor-stimulated, ERK1/2-dependent BimEL turnover proceeds normally in Cbl-containing or Cbl-/- fibroblasts. These results indicate that Cbl is not required for ERK1/2-dependent BimEL turnover in fibroblasts and epithelial cells and any role it has in other cell types is likely to be indirect.

Original languageEnglish (US)
Pages (from-to)2605-2611
Number of pages7
JournalCellular Signalling
Volume19
Issue number12
DOIs
StatePublished - Dec 1 2007

Fingerprint

Phosphorylation
Tyrosine
Phosphoproteins
Fibroblasts
TYK2 Kinase
Ubiquitin-Protein Ligases
Ubiquitination
Proteasome Endopeptidase Complex
Serine
Intercellular Signaling Peptides and Proteins
Epithelial Cells
Proteins

Keywords

  • Bim
  • Cbl
  • ERK1/2
  • Proteasome
  • Ubiquitin ligase

ASJC Scopus subject areas

  • Cell Biology

Cite this

c-Cbl is not required for ERK1/2-dependent degradation of BimEL. / Wiggins, Ceri M.; Band, Hamid; Cook, Simon J.

In: Cellular Signalling, Vol. 19, No. 12, 01.12.2007, p. 2605-2611.

Research output: Contribution to journalArticle

Wiggins, Ceri M. ; Band, Hamid ; Cook, Simon J. / c-Cbl is not required for ERK1/2-dependent degradation of BimEL. In: Cellular Signalling. 2007 ; Vol. 19, No. 12. pp. 2605-2611.
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