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PNAS 99 (8): 5406-5411

Copyright © 2002 by the National Academy of Sciences.


BIOLOGICAL SCIENCES / CELL BIOLOGY

Modulation of protein translation by Nck-1

Sem Kebache*, Dongmei Zuo*, Eric Chevet{dagger}, and Louise Larose*,{ddagger}

Departments of *Medicine and {dagger}Surgery, Polypeptide Laboratory, Division of Endocrinology, McGill University, Montreal, QC, Canada H3A 2B2

Received for publication September 13, 2001.

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 β subunit of the eukaryotic initiation factor 2 (eIF2β). Binding of eIF2β was specific to the SH3 domains of Nck-1, and in vivo, the interaction Nck/eIF2β was demonstrated by reciprocal coimmunoprecipitations. In addition, Nck was detected in a molecular complex with eIF2β 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 eIF2β. 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.


{ddagger} To whom reprint requests should be addressed. E-mail: louise.larose{at}mcgill.ca.

Edited by Lewis Clayton Cantley, Beth Israel Deaconess Medical Center, Boston, MA, and approved February 12, 2002

This paper was submitted directly (Track II) to the PNAS office.


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