Increased SOCS6 stability with PMA requires its N-terminal region and the Erk pathway via Pkcdelta activation.
We investigated stability of the ectopically expressed the SOCS6 protein in HEK293T cells with PMA, which activates protein kinase C (PKC). The treatment of PMA could largely increase SOCS6 stability in HEK293T cells. But, we did not observe increased protein levels of SOCS3 or Erk1 with PMA. This result suggests that the increased stability of SOCS6 with PMA did not generally occur in other proteins. The stability of SOCS6 depended on the N-terminal region containing an unidentified domain. We then studied the role of signal pathways in SOCS6 stability with PMA. We found that both Erk and Pkcdelta activation were required for the increased SOCS6 stability by PMA. The Erk activation by PMA appeared to be downstream from the Pkcdelta activation. The increased SOCS6 stability and Erk activation by PMA were both conserved in another cell line, MCF7. In addition, we demonstrated that PMA, insulin, and PDGF increased both the stability of endogenous-expressed SOCS6 and Erk activation in MDA-MB231 cells. These observations suggest that Erk activation may be correlated in the cells with high expression of SOCS6.
Hwang
Mi-Na
MN
Research Institute, National Cancer Center, 809 Madu 1-dong, Ilsan-gu, Goyang-si Gyeonggi-do 411-764, Republic of Korea.
Ha
Tae Hun
TH
Park
Jongsun
J
Shim
Jaegal
J
Lee
Ho
H
Kim
Young-Nyun
YN
Lee
Eun Sook
ES
Yoon
Sungpil
S
D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D051745:Protein Kinase C-delta / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D050826:Suppressor of Cytokine Signaling Proteins / Q000737:chemistry* / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage*
C473085:SOCS6 protein, human; D050826:Suppressor of Cytokine Signaling Proteins; D051745:Protein Kinase C-delta; D048049:Extracellular Signal-Regulated MAP Kinases; D013755:Tetradecanoylphorbol Acetate