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.
Division of Chemistry and Molecular Engineering, Seoul National University, Seoul 151-742, Korea.
Hyung Suk
HS
Oh
Haeyoung
H
Kwon
Suk Kyun
SK
Sun
Chul-Hak
CH
Yang
D002352:Carrier Proteins / Q000494:pharmacology*; D002454:Cell Differentiation; D003593:Cytoplasm / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D010455:Peptides / Q000737:chemistry; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051575:Proto-Oncogene Proteins c-yes; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000080882:Ribosomal Protein L10; D012269:Ribosomal Proteins; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured; D020798:Two-Hybrid System Techniques; D018909:src Homology Domains; D019061:src-Family Kinases
D002352:Carrier Proteins; D018076:DNA, Complementary; C000715470:MAS1 protein, human; D010455:Peptides; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C000630686:RPL10 protein, human; D012269:Ribosomal Proteins; D004247:DNA; D005982:Glutathione Transferase; D051575:Proto-Oncogene Proteins c-yes; D019061:src-Family Kinases