-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Protein kinase CK2 is a pleiotropic enzyme which is ubiquitously expressed in eukaryotic cells. Several years ago CK2 was found to be associated with the mammalian endoplasmic reticulum. So far nothing is known about the function of CK2 at the ER. METHODS: CK2 phosphorylation sites in the polypeptide chain of Sec63 were mapped using deletion mutants and a peptide library. Binding of Sec63 to CK2 and to Sec62 was analysed by pull-down assays and by co-immunoprecipitation RESULTS: Sec63 was identified as a novel substrate and binding partner of protein kinase CK2. We identified serine 574, serine 576 and serine 748 as CK2 phosphorylation sites. Phosphorylation of Sec63 by CK2 enhanced its binding to Sec62. CONCLUSIONS: Protein kinase CK2 phosphorylation of Sec63 leads to an enhanced binding of Sec63 to Sec62. This complex formation is a prerequisite for a functional ER protein translocon. GENERAL SIGNIFICANCE: Thus, our present data indicate a regulatory role of CK2 in the ER protein translocation.
Biochimica et Biophysica Acta 02/2013; 1830(4):2938-2945. · 4.66 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The formation of multiple cysts in one or several organs is a characteristic of several human inherited diseases. Recent research suggests that problems in planar cell polarity may be the common denominator in polycystic diseases. Mutations in at least two genes are linked to autosomal dominant polycystic liver disease (PCLD), PRKCSH and SEC63. A recent study linked PRKCSH to the signaling- and cytoskeletal adaptor-component β-catenin. In a yeast two hybrid screen we identified the cytosolic protein nucleoredoxin (NRX) as an interaction partner of human Sec63. Since NRX is involved in the Wnt signaling pathways, we characterized this interaction. Thus, Sec63 is linked to the Wnt signaling pathways and this interaction may be the reason why mutations in SEC63 can lead to PCLD.
FEBS letters 02/2011; 585(4):596-600. · 3.54 Impact Factor
-
Linda Müller,
Maria Diaz de Escauriaza,
Patrick Lajoie,
Melanie Theis,
Martin Jung,
Anika Müller,
Carsten Burgard,
Markus Greiner,
Erik L Snapp,
Johanna Dudek,
Richard Zimmermann
[show abstract]
[hide abstract]
ABSTRACT: Because of similarity to their yeast orthologues, the two membrane proteins of the human endoplasmic reticulum (ER) Sec62 and Sec63 are expected to play a role in protein biogenesis in the ER. We characterized interactions between these two proteins as well as the putative interaction of Sec62 with ribosomes. These data provide further evidence for evolutionary conservation of Sec62/Sec63 interaction. In addition, they indicate that in the course of evolution Sec62 of vertebrates has gained an additional function, the ability to interact with the ribosomal tunnel exit and, therefore, to support cotranslational mechanisms such as protein transport into the ER. This view is supported by the observation that Sec62 is associated with ribosomes in human cells. Thus, the human Sec62/Sec63 complex and the human ER membrane protein ERj1 are similar in providing binding sites for BiP in the ER-lumen and binding sites for ribosomes in the cytosol. We propose that these two systems provide similar chaperone functions with respect to different precursor proteins.
Molecular biology of the cell 03/2010; 21(5):691-703. · 5.98 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Transport into the endoplasmic reticulum (ER) is the crucial step in the biosynthesis of most secretory proteins and many membrane proteins. The products of the SIL1, SEC62 and SEC63 genes act in concert with the SEC61 complex and the molecular chaperones BiP and GRP170 to transport proteins into the ER. Interestingly, recent genetic work has linked mutations in the human and murine SIL1 genes to neurodegeneration, and mutations in the human SEC63 gene to autosomal dominant polycystic liver disease. Furthermore, mutations in the SEC63 gene and overexpression of the SEC62 gene are associated with various human cancers. Therefore, we suggest that these diseases should be considered to be pathologies of protein transport into the ER rather than protein-folding diseases.
Trends in Molecular Medicine 01/2007; 12(12):567-73. · 10.35 Impact Factor
