NM23H2 inhibits EGF- and Ras-induced proliferation of NIH3T3 cells by blocking the ERK pathway.
The NM23 family proteins are involved in a variety of biological processes including tumor metastasis, development, and differentiation; however, their functions in the regulation of cellular proliferation are poorly understood. We have investigated the role of one NM23 family protein, NM23H2, in the regulation of cellular proliferation directed by the extracellular signal regulated kinase (ERK) pathway. The activity of ERKs was enhanced by knockdown of endogenous NM23H2 and blocked by overexpression of NM23H2 in both NIH3T3 and HEK293 cells. Additionally, the epidermal growth factor (EGF)- and oncogenic Ras(G12R)-induced proliferation of both HEK293 and NIH3T3 cells was reduced by NM23H2 overexpression. Furthermore, activation of Raf-1, MEK and the ERKs by either EGF or Ras(G12R) was inhibited by NM23H2 overexpression. Together, our data indicate that NM23H2 is a negative regulator of cellular proliferation stimulated by EGF- and Ras-mediated activation of the ERK pathway.
Lee
Mi-Young
MY
Department of Biotechnology, Protein Network Research Center, Yonsei University, 134 Shinchon-Dong, Seodemun-Gu, Seoul, Republic of Korea.
Jeong
Woo-Jeong
WJ
Oh
Jong-Won
JW
Choi
Kang-Yell
KY
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation; D017931:DNA Primers; D004815:Epidermal Growth Factor / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D054778:NM23 Nucleoside Diphosphate Kinases / Q000502:physiology*; D015689:Oncogene Protein p21(ras) / Q000502:physiology*
D017931:DNA Primers; D054778:NM23 Nucleoside Diphosphate Kinases; D004815:Epidermal Growth Factor; D048049:Extracellular Signal-Regulated MAP Kinases; D015689:Oncogene Protein p21(ras)