The Shb signalling scaffold binds to and regulates constitutive signals from the Epstein-Barr virus LMP2A membrane protein.
Oncogene
; 26(34): 4908-17, 2007 Jul 26.
Article
in En
| MEDLINE
| ID: mdl-17311000
ABSTRACT
The Epstein-Barr virus latency-associated membrane protein LMP2A has been shown to activate the survival kinase Akt in epithelial and B cells in a phosphoinositide 3-kinase-dependent fashion. In this study, we demonstrate that the signalling scaffold Shb associates through SH2 and PTB domain interactions with phosphorylated tyrosine motifs in the LMP2A N-terminal tail. Additionally, we show that mutation of tyrosines in these motifs as well as shRNA-mediated downregulation of Shb leads to a loss of constitutive Akt-activation in LMP2A-expressing cells. Furthermore, utilization by Shb of the LMP2A ITAM motif regulates stability of the Syk tyrosine kinase in LMP2A-expressing cells. Our data set the precedent for viral utilization of the Shb signalling scaffold and implicate Shb as a regulator of LMP2A-dependent Akt activation.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
B-Lymphocytes
/
Signal Transduction
/
Viral Matrix Proteins
/
Proto-Oncogene Proteins
/
Adaptor Proteins, Signal Transducing
Limits:
Humans
Language:
En
Journal:
Oncogene
Journal subject:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Year:
2007
Document type:
Article
Affiliation country:
Sweden