1995
DOI: 10.1091/mbc.6.3.237
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Biochemical and biological analysis of Mek1 phosphorylation site mutants.

Abstract: Recently, we described the constitutive activation of Mek1 by mutation of its two serine phosphorylation sites. We have now characterized the biochemical properties of these Mek1 mutants and performed microinjection experiments to investigate the effect of an activated Mek on oocyte maturation. Single acidic substitution of either serine 218 or 222 activated Mek1 by 10-50 fold. The double acidic substitutions, [Asp218, Asp222] and [Asp218, Glu222], activated Mek1 over 6000-fold. The specific activity of the [A… Show more

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Cited by 113 publications
(111 citation statements)
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“…Thus, their results may be consistent with our tentative hypothesis of a positive feedback loop. In contrast, in the experiments of Huang et al (62), cycloheximide treatment did not affect markedly the active MAPKK-induced activation of MAPK. Although the apparent difference between these observations cannot be easily explained, the possible difference in the strength of upstream activating enzymes for MAPK (e.g.…”
Section: Fig 3 Initiation Of Oocyte Maturation By Ste11 and Effectsmentioning
confidence: 56%
See 1 more Smart Citation
“…Thus, their results may be consistent with our tentative hypothesis of a positive feedback loop. In contrast, in the experiments of Huang et al (62), cycloheximide treatment did not affect markedly the active MAPKK-induced activation of MAPK. Although the apparent difference between these observations cannot be easily explained, the possible difference in the strength of upstream activating enzymes for MAPK (e.g.…”
Section: Fig 3 Initiation Of Oocyte Maturation By Ste11 and Effectsmentioning
confidence: 56%
“…After completion of this study, two reports (62, 63) appeared demonstrating that injection of an active MAPKK mutant (62) or thiophosphorylated MAPK (63) is capable of inducing GVBD in Xenopus oocytes in the absence of progesterone. Moreover, it has been demonstrated that injection of thiophosphorylated MAPK induces activation of endogenous MAPK and that this activation is inhibited by cycloheximide treatment (63).…”
Section: Fig 3 Initiation Of Oocyte Maturation By Ste11 and Effectsmentioning
confidence: 99%
“…The structure and function relationship of these kinases has been widely studied using MKK1 and MKK2 as prototypic kinases (Wu et al, 1993;Brott et al, 1993;Pages et al, 1994). Selective mutations inhibiting either of the kinase activities have been shown to disrupt the signaling function of the respective signaling module (Brott et al, 1993;Pages et al, 1994;Huang et al, 1995). Of the known kinase signaling modules, only those involved in the activation of the extracellular-signal regulated kinases 1 and 2 (ERK1 and ERK2) are more thoroughly characterized.…”
Section: Superfamily Of Dual-speci®city Kinasesmentioning
confidence: 99%
“…For several years, it has been clear that constitutively active Ras and Raf are capable of inducing cell growth whereas recent work from several laboratories shows that constitutively active MKK can induce NIH 3T3 cell growth and transformation (Brunet et al, 1994;Cowley et al, 1994;Mansour et al, 1994), differentiation of PC12 cells (Cowley et al, 1994), and Xenopus oocyte maturation (Huang et al, 1995). The fact that active MKK has the same effects as active versions of upstream molecules like Raf-1 or Ras implies that the sequential pathway Ras -> Raf-1 -> MKK -> ERK is sufficient to induce growth or differentiation of mammalian cells.…”
Section: Introductionmentioning
confidence: 99%