Gewählte Publikation:
Stumptner, C; Heid, H; Zatloukal, K; Fuchsbichler, A; Hauser, H; Denk, H.
Identification of p62, a phosphotyrosine independent ligand of p56lck kinase, as a major component of intracytoplasmic hyaline bodies in hepatocellular carcinoma.
Verh Dtsch Ges Pathol. 1999; 83: 254-259.
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- Führende Autor*innen der Med Uni Graz
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Stumptner Cornelia
- Co-Autor*innen der Med Uni Graz
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Hauser Hubert
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Zatloukal Kurt
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- Abstract:
- Intracytoplasmic hyaline bodies (IHBs) resemble a peculiar type of cytoplasmic inclusions in cells of hepatocellular carcinoma (HCC) which so far have escaped further characterization. In order to determine protein composition of IHBs we investigated tissue of a HCC containing numerous IHBs by immunohistochemistry and Western blot analysis using a large panel of different antibodies. Our studies revealed immunoreactivity of IHBs with the monoclonal antibodies SMI 31 and MPM-2 which recognize hyperphosphorylated epitopes present on paired helical filaments in Alzheimer's disease brains (SMI 31) and on proteins hyperphosphorylated by mitotic kinases (MPM-2), respectively. In two-dimensional Western blots of HCC extracts SMI 31 and MPM-2 antibodies detected a 62 to 65 kD protein with an isoelectric point around 4.5. Microsequencing identified this protein as p62, a recently identified phosphotyrosine-independent ligand of the SH2 domain of tyrosine kinase p56lck. Immunoreactivity of p62 protein spots with antibodies to phosphorylated epitopes (i.e. SMI 31 and MPM-2) suggest that p62 is highly phosphorylated in IHBs. This is the first report on accumulation of p62 as cellular inclusions and its association with human disease.
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Amino Acid Sequence -
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Antibodies, Monoclonal -
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Antigens, Neoplasm - analysis
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Carcinoma, Hepatocellular - enzymology
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Cytoplasm - pathology
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Humans - pathology
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Inclusion Bodies - enzymology
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Liver Neoplasms - enzymology
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - metabolism
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Molecular Sequence Data - metabolism
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Phosphotyrosine - metabolism
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RNA-Binding Proteins - analysis