TY - JOUR
T1 - Reversion-induced LIM interaction with Src reveals a novel Src inactivation cycle
AU - Zhang, Yongjun
AU - Tu, Yizeng
AU - Zhao, Jianping
AU - Chen, Ka
AU - Wu, Chuanyue
PY - 2009/3/23
Y1 - 2009/3/23
N2 - Aberrant Src activation plays prominent roles in cancer progression. However, how Src is activated in cancer cells is largely unknown. Genetic Src-activating mutations are rare and, therefore, are insufficient to account for Src activation commonly found in human cancers. In this study, we show that reversion-induced LIM (RIL), which is frequently lost in colon and other cancers as a result of epigenetic silencing, suppresses Src activation. Mechanistically, RIL suppresses Src activation through interacting with Src and PTPL1, allowing PTPL Idependent dephosphorylation of Src at the activation loop. Importantly, the binding of RIL to Src is drastically reduced upon Src inactivation. Our results reveal a novel Src inactivation cycle in which RIL preferentially recognizes active Src and facilitates PTPL1-mediated inactivation of Src. Inactivation of Src, in turn, promotes dissociation of RIL from Src, allowing the initiation of a new Src in-activation cycle. Epigenetic silencing of RIL breaks this Src inactivation cycle and thereby contributes to aberrant Src activation in human cancers.
AB - Aberrant Src activation plays prominent roles in cancer progression. However, how Src is activated in cancer cells is largely unknown. Genetic Src-activating mutations are rare and, therefore, are insufficient to account for Src activation commonly found in human cancers. In this study, we show that reversion-induced LIM (RIL), which is frequently lost in colon and other cancers as a result of epigenetic silencing, suppresses Src activation. Mechanistically, RIL suppresses Src activation through interacting with Src and PTPL1, allowing PTPL Idependent dephosphorylation of Src at the activation loop. Importantly, the binding of RIL to Src is drastically reduced upon Src inactivation. Our results reveal a novel Src inactivation cycle in which RIL preferentially recognizes active Src and facilitates PTPL1-mediated inactivation of Src. Inactivation of Src, in turn, promotes dissociation of RIL from Src, allowing the initiation of a new Src in-activation cycle. Epigenetic silencing of RIL breaks this Src inactivation cycle and thereby contributes to aberrant Src activation in human cancers.
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U2 - 10.1083/jcb.200810155
DO - 10.1083/jcb.200810155
M3 - Article
C2 - 19307596
AN - SCOPUS:64049113181
SN - 0021-9525
VL - 184
SP - 785
EP - 792
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 6
ER -