Format

Send to

Choose Destination
See comment in PubMed Commons below
Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5406-11.

Modulation of protein translation by Nck-1.

Author information

1
Departments of Medicine and Surgery, Polypeptide Laboratory, Division of Endocrinology, McGill University, Montreal, QC, Canada H3A 2B2.

Abstract

In mammals, Nck represented by two genes, is a 47-kDa SH2/SH3 domain-containing protein lacking intrinsic enzymatic function. Here, we reported that the first and the third SH3 domains of Nck-1 interact with the C-terminal region of the beta subunit of the eukaryotic initiation factor 2 (eIF2 beta). Binding of eIF2 beta was specific to the SH3 domains of Nck-1, and in vivo, the interaction Nck/eIF2 beta was demonstrated by reciprocal coimmunoprecipitations. In addition, Nck was detected in a molecular complex with eIF2 beta in an enriched ribosomal fraction, whereas no other SH2/SH3 domain-containing adapters were found. Cell fractionation studies demonstrated that the presence of Nck in purified ribosomal fractions was enhanced after insulin stimulation, suggesting that growth factors dynamically regulate translocation of Nck to ribosomes. In HEK293 cells, we observed that transient overexpression of Nck-1 significantly enhanced Cap-dependent and -independent protein translation. This effect of Nck-1 required the integrity of its first and third SH3 domains originally found to interact with eIF2 beta. Finally, in vitro, Nck-1 also increased protein translation, revealing a direct role for Nck-1 in this process. Our study demonstrates that in addition to mediate receptor tyrosine kinase signaling, Nck-1 modulates protein translation potentially through its direct interaction with an intrinsic component of the protein translation machinery.

PMID:
11959995
PMCID:
PMC122782
DOI:
10.1073/pnas.082483399
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center