TY - JOUR
T1 - Deregulation of DUSP activity in EGFR-mutant lung cancer cell lines contributes to sustained ERK1/2 signaling
AU - Britson, Joel S.
AU - Barton, Frederick
AU - Balko, Justin M.
AU - Black, Esther P.
PY - 2009/12/18
Y1 - 2009/12/18
N2 - Lung cancers demonstrate loss of cellular signaling control pathways. EGFR-mutant non-small cell lung cancer cell lines constitutively express active ERK1/2 and require ERK activity for survival. DUSP4 is a negative regulator of ERK activity and is up-regulated in EGFR-mutant lung cancer cell lines relative to K-ras mutant cells. Both DUSP4 and family member, DUSP1, can bind ERK in vitro. However, only DUSP1 has detectable binding to ERK in vivo in cell lines of either genotype. Depletion of DUSP4 in EGFR-mutant cells unexpectedly results in loss of pERK whereas loss of DUSP4 in K-ras mutant cells predictably yields increased pERK. These data support a role for DUSP4, and perhaps DUSP1, as a positive activator of ERK in EGFR-mutant lung cancer cell lines independent of the ability to bind to ERK.
AB - Lung cancers demonstrate loss of cellular signaling control pathways. EGFR-mutant non-small cell lung cancer cell lines constitutively express active ERK1/2 and require ERK activity for survival. DUSP4 is a negative regulator of ERK activity and is up-regulated in EGFR-mutant lung cancer cell lines relative to K-ras mutant cells. Both DUSP4 and family member, DUSP1, can bind ERK in vitro. However, only DUSP1 has detectable binding to ERK in vivo in cell lines of either genotype. Depletion of DUSP4 in EGFR-mutant cells unexpectedly results in loss of pERK whereas loss of DUSP4 in K-ras mutant cells predictably yields increased pERK. These data support a role for DUSP4, and perhaps DUSP1, as a positive activator of ERK in EGFR-mutant lung cancer cell lines independent of the ability to bind to ERK.
KW - MAPK
KW - Phosphatase
KW - Signal transduction
UR - http://www.scopus.com/inward/record.url?scp=70449732108&partnerID=8YFLogxK
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U2 - 10.1016/j.bbrc.2009.10.061
DO - 10.1016/j.bbrc.2009.10.061
M3 - Article
C2 - 19836351
AN - SCOPUS:70449732108
SN - 0006-291X
VL - 390
SP - 849
EP - 854
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -