Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

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.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Deletion of Nck1 attenuates hepatic ER stress signaling and improves glucose tolerance and insulin signaling in liver of obese mice.
M. Latreille, M.-K. Laberge, G. Bourret, L. Yamani, and L. Larose (2011)
Am J Physiol Endocrinol Metab 300, E423-E434
   Abstract »    Full Text »    PDF »
p21-Activated kinases regulate actin remodeling in glomerular podocytes.
J. Zhu, O. Attias, L. Aoudjit, R. Jiang, H. Kawachi, and T. Takano (2010)
Am J Physiol Renal Physiol 298, F951-F961
   Abstract »    Full Text »    PDF »
Src homology domain 2 adaptors affect adherence of Salmonella enterica serovar Typhimurium to non-phagocytic cells.
E. C. Boyle, N. F. Brown, J. H. Brumell, and B. B. Finlay (2007)
Microbiology 153, 3517-3526
   Abstract »    Full Text »    PDF »
Molecular Mechanisms of RET Receptor-Mediated Oncogenesis in Multiple Endocrine Neoplasia 2B..
T. S. Gujral, V. K. Singh, Z. Jia, and L. M. Mulligan (2006)
Cancer Res. 66, 10741-10749
   Abstract »    Full Text »    PDF »
Nck in a Complex Containing the Catalytic Subunit of Protein Phosphatase 1 Regulates Eukaryotic Initiation Factor 2{alpha} Signaling and Cell Survival to Endoplasmic Reticulum Stress.
M. Latreille and L. Larose (2006)
J. Biol. Chem. 281, 26633-26644
   Abstract »    Full Text »    PDF »
The adaptor protein Nck interacts with Fas ligand: Guiding the death factor to the cytotoxic immunological synapse.
M. Lettau, J. Qian, A. Linkermann, M. Latreille, L. Larose, D. Kabelitz, and O. Janssen (2006)
PNAS 103, 5911-5916
   Abstract »    Full Text »    PDF »
Tyrosine phosphorylation acts as a molecular switch to full-scale activation of the eIF2alpha} RNA-dependent protein kinase..
Q. Su, S. Wang, D. Baltzis, L.-K. Qu, A. H.-T. Wong, and A. E. Koromilas (2006)
PNAS 103, 63-68
   Abstract »    Full Text »    PDF »
Ribotoxic Stress Response to the Trichothecene Deoxynivalenol in the Macrophage Involves the Src Family Kinase Hck.
H.-R. Zhou, Q. Jia, and J. J. Pestka (2005)
Toxicol. Sci. 85, 916-926
   Abstract »    Full Text »    PDF »
Nck-dependent Activation of Extracellular Signal-regulated Kinase-1 and Regulation of Cell Survival during Endoplasmic Reticulum Stress.
D. T. Nguyen, S. Kebache, A. Fazel, H. N. Wong, S. Jenna, A. Emadali, E.-h. Lee, J. J.M. Bergeron, R. J. Kaufman, L. Larose, et al. (2004)
Mol. Biol. Cell 15, 4248-4260
   Abstract »    Full Text »    PDF »
Nck-1 Antagonizes the Endoplasmic Reticulum Stress-induced Inhibition of Translation.
S. Kebache, E. Cardin, D. T. Nguyen, E. Chevet, and L. Larose (2004)
J. Biol. Chem. 279, 9662-9671
   Abstract »    Full Text »    PDF »
The Adaptor Protein Nck-1 Couples the Netrin-1 Receptor DCC (Deleted in Colorectal Cancer) to the Activation of the Small GTPase Rac1 through an Atypical Mechanism.
X. Li, M. Meriane, I. Triki, M. Shekarabi, T. E. Kennedy, L. Larose, and N. Lamarche-Vane (2002)
J. Biol. Chem. 277, 37788-37797
   Abstract »    Full Text »    PDF »
Identification of candidate lung cancer susceptibility genes in mouse using oligonucleotide arrays.
W J Lemon, H Bernert, H Sun, Y Wang, and M You (2002)
J. Med. Genet. 39, 644-655
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882