TY - JOUR
T1 - Differential regulation of mitogen-activated protein/ERK kinase (MEK)1 and MEK2 and activation by a Ras-independent mechanism
AU - Xu, Shuichan
AU - Khoo, Shih
AU - Dang, Alphonsus
AU - Witt, Sarah
AU - Do, Vuong
AU - Zhen, Erzhen
AU - Schaefer, Erik M.
AU - Cobb, Melanie H.
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 1997
Y1 - 1997
N2 - Mitogen-activated protein (MAP)/ERK kinase (MEK) 1 and MEK2 are the upstream activators of the MAP kinases, ERK1 and ERK2. MEK1 and MEK2 are ~85% identical in sequence but have unique inserts in their C-terminal domains. MEK isoform-specific antibodies were used to examine expression and regulation of each enzyme. MEK1 and MEK2 were expressed in approximately equal amounts in several cell lines; in some, MEK1 was present in slight excess. Activation of tyrosine kinase-containing receptors, heterotrimeric G proteins, and protein kinase C enhanced the activities of both MEK isoforms in 293 and PC12 cells. AIF4- stimulated both MEK1 and MEK2 in PC12 cells expressing a dominant interfering Ras mutant that prevents nerve growth factor-dependent activation of the cascade. Carbachol also stimulated the pathway in these cells. Thus, in addition to their ability to activate Ras/Raf and the downstream ERK pathway, heterotrimeric G proteins also appear to trigger a Ras-independent mechanism to regulate this kinase cascade. In U373, Chinese hamster ovary (CHO), and INS-1 cells, MEK1 was activated by regulators of ERKs, while MEK2 was not. These data suggest that, like the MAP kinases ERK1 and ERK2, in some cell settings the two similar MEK isoforms are differentially regulated.
AB - Mitogen-activated protein (MAP)/ERK kinase (MEK) 1 and MEK2 are the upstream activators of the MAP kinases, ERK1 and ERK2. MEK1 and MEK2 are ~85% identical in sequence but have unique inserts in their C-terminal domains. MEK isoform-specific antibodies were used to examine expression and regulation of each enzyme. MEK1 and MEK2 were expressed in approximately equal amounts in several cell lines; in some, MEK1 was present in slight excess. Activation of tyrosine kinase-containing receptors, heterotrimeric G proteins, and protein kinase C enhanced the activities of both MEK isoforms in 293 and PC12 cells. AIF4- stimulated both MEK1 and MEK2 in PC12 cells expressing a dominant interfering Ras mutant that prevents nerve growth factor-dependent activation of the cascade. Carbachol also stimulated the pathway in these cells. Thus, in addition to their ability to activate Ras/Raf and the downstream ERK pathway, heterotrimeric G proteins also appear to trigger a Ras-independent mechanism to regulate this kinase cascade. In U373, Chinese hamster ovary (CHO), and INS-1 cells, MEK1 was activated by regulators of ERKs, while MEK2 was not. These data suggest that, like the MAP kinases ERK1 and ERK2, in some cell settings the two similar MEK isoforms are differentially regulated.
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U2 - 10.1210/mend.11.11.0010
DO - 10.1210/mend.11.11.0010
M3 - Article
C2 - 9328344
AN - SCOPUS:0030760981
SN - 0888-8809
VL - 11
SP - 1618
EP - 1625
JO - Molecular Endocrinology
JF - Molecular Endocrinology
IS - 11
ER -