QM, a Putative Tumor Suppressor, Regulates Proto-oncogene c-Yes

Hyung Suk Oh,Haeyoung Kwon,Suk Kyun Sun,Chul-Hak Yang

doi:10.1074/jbc.m201859200

Hyung Suk Oh, Haeyoung Kwon + Show 2 more

Open Access

https://doi.org/10.1074/jbc.m201859200

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Abstract

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.

Highlights

Src family kinases are involved in many intracellular functions, including cell stability, division, proliferation, migration, and differentiation. c-Yes is one of the Src family kinases and is expressed ubiquitously in most tissues and presumably is involved in many signaling pathways [1]. c-Yes has not been studied extensively compared with other members of Src families because of the high similarity to Src
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
It has been revealed that two regions of the QM protein are bound to the SH3 domain of c-Yes (Fig. 2, A and B)

Summary

Introduction

Src family kinases are involved in many intracellular functions, including cell stability, division, proliferation, migration, and differentiation. c-Yes is one of the Src family kinases and is expressed ubiquitously in most tissues and presumably is involved in many signaling pathways [1]. c-Yes has not been studied extensively compared with other members of Src families because of the high similarity to Src. 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.

Results

Conclusion