QM, a putative tumor suppressor, regulates proto-oncogene c-yes.
The QM gene encodes a 24.5 kDa ribosomal protein L10 known to be highly homologous to a Jun-binding protein (Jif-1), which inhibits the formation of Jun-Jun dimers. Here we have carried out screening with the c-Yes protein and found that a QM homologous protein showed interactions with c-Yes and other ... Src family members. We have found that two different regions of QM protein were associated with the SH3 domain of c-Yes. The QM protein does not contain canonical SH3 binding motifs or previously reported amino acid fragments showing interaction with SH3 domains. Several c-Yes kinase activity assays indicated that the QM protein reduced c-Yes kinase activity by 70% and that this suppression is related not only to the two SH3 binding regions but also to the C-terminal region of QM. Moreover, our autophosphorylation assays clarified that this regulation resulted from the inhibition of c-Yes autophosphorylation. Immunofluorescence studies showed that the QM proteins and c-Yes are able to interact in various tumor cell lines in vivo. The increases of the c-Yes protein and mRNA levels were detected when the QM was transfected. These results suggest that the QM protein might be a regulator for various signal transduction pathways involving SH3 domain-containing membrane proteins.
Mesh Terms:
Carrier Proteins, Cell Differentiation, Cytoplasm, Cytosol, DNA, DNA, Complementary, Dose-Response Relationship, Drug, Gene Expression Regulation, Neoplastic, Glutathione Transferase, Hela Cells, Humans, Microscopy, Fluorescence, Models, Genetic, Peptides, Phosphorylation, Precipitin Tests, Protein Binding, Protein Structure, Tertiary, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-yes, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction, Ribosomal Proteins, Signal Transduction, Transfection, Tumor Cells, Cultured, Two-Hybrid System Techniques, src Homology Domains, src-Family Kinases
Carrier Proteins, Cell Differentiation, Cytoplasm, Cytosol, DNA, DNA, Complementary, Dose-Response Relationship, Drug, Gene Expression Regulation, Neoplastic, Glutathione Transferase, Hela Cells, Humans, Microscopy, Fluorescence, Models, Genetic, Peptides, Phosphorylation, Precipitin Tests, Protein Binding, Protein Structure, Tertiary, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-yes, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction, Ribosomal Proteins, Signal Transduction, Transfection, Tumor Cells, Cultured, Two-Hybrid System Techniques, src Homology Domains, src-Family Kinases
J. Biol. Chem.
Date: Sep. 27, 2002
PubMed ID: 12138090
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