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Studies on components involved in the Degradation of Misfolded Glycoproteins
Author(s) -
Li Guangtao,
zhao Gang,
zhou Xiaoke,
Schindelin hermann,
Lennarz William J.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.604.3
Subject(s) - phosphorylation , endoplasmic reticulum associated protein degradation , ubiquitin ligase , endoplasmic reticulum , microbiology and biotechnology , tyrosine phosphorylation , glycoprotein , biochemistry , tyrosine , biology , proto oncogene tyrosine protein kinase src , ubiquitin , chemistry , unfolded protein response , gene
In eukaryotic cells, the endoplasmic reticulum associated degradation (ERAD) pathway is essential for degradation of misfolded glycoproteins. Initially, we found that a higher order complex consisting of interactions between the ER bound E3 ligase gp78, mp97, mPNGase and mHR23B. This complex may serve to route misfolded glycoproteins out of the ER where they are degraded by the proteasome. In this complex, mp97 functions as an organizer to interact with E3 ligase mp78 and mPNGase. Recently, we found a novel protein binding motif of mp97 consisting of its last ten amino acid residues, which is both essential and sufficient to mediate mp97's interaction with mPNGase and Ufd3. Phosphorylation of mp97's highly conserved penultimate tyrosine residue, the main phosphorylation site during T‐cell receptor stimulation, completely blocks binding of either PNGase or Ufd3 to mp97. We also found that overexpression of the tyrosine kinase Src significantly increased the phosphorylation level of p97 and caused accumulation of the ERAD substrate TCRα‐GFP. Furthermore, an in vitro phosphorylation assay showed that Src directly phosphorylated p97. All these results indicate that phosphorylation of p97 may modulate its function. Further studies on the role of the phosphorylation of p97 in its function are underway.