Extracellular Signal-Regulated Protein Kinases (ERKS) 1, 2, and 3

The extracellular-signal-regulated protein kinases (Erks) are required for UV-induced AP-1 activation in JB6 cells

“…The signal transduction pathways leading to transcription factor activation have been extensively studied in the last several years (Boulton et al, 1990(Boulton et al, , 1991Kallunki et al, 1994;Kyriakis et al, 1994;Robbins et al, 1993). It is known that mammalian cells contain at least three signaling pathways which are structurally related to the MAPKs pathway.…”

“…The activation of MAPKs may be by translocation to the nucleus, where these kinases phosphorylate target transcription factors such as AP-1 (Coso et al, 1995;Huang et al, 1996a;Rosenberger and Bowden, 1996). It is believed that Erks are strongly activated and play a critical role in transmitting signals initiated by 12-0-tetradecanoylphorbol-13-acetate (TPA) and growth factors such as epidermal growth factor (EGF), platelet-derived growth factor (PDGF) (Cowley et al, 1994;Dalton and Treisman, 1992;L'Allemain et al, 1992;PageÁ s et al, 1993;Robbins et al, 1993;Wan et al, 1996;Xia et al, 1995). Whereas the JNKs/SAPKs and P38 kinases are potently activated by various forms of stress, such as ultraviolet light (UV), heat shock and in¯ammation (Adler et al, 1995(Adler et al, , 1996BuÈ scher et al, 1988; Denhardt, 1996;Ludwig et al, 1996;Minden et al, 1994; Sa nchez et al, 1994), the activation of these pathways is not mutually exclusive.…”

Cot protooncoprotein activates the dual specificity kinases MEK-1 and SEK-1 and induces differentiation of PC12 cells

“…The measured luciferase activity was twofold higher than the activity induced by an equal amount of c-Raf-1-BXB DNA. To analyse whether this Cot mediated promoter activation is dependent on the ERK pathway, 293 cells were transfected with a dominant negative mutant of ERK (ERKB3 K52/R52) (Robbins et al, 1993) in combination with Cot and the reporter-construct. The mutant was able to inhibit the Cot mediated promoter activation by 80% suggesting that the ERK pathway was required for the Cot mediated activation of the Ap-1-and Etsdriven promoter (Figure 4a).…”

“…Samples were resuspended in 30 ml of kinase bu er containing 5 mCi [g-32 P]ATP (3000 Ci/mM, Amersham) and 4 mg of recombinant K97M kinase dead MEK mutant protein (MEK-kinase assay), 4 mg of recombinant K167R kinase dead GST-SEK mutant protein or a kinasedead ERK mutant protein and incubated at 308C for 15 min. A coupled assay was performed in the presence of 2 mg GST-MEK and 2 mg of the kinase-dead ERK mutant (Robbins et al, 1993;Alessi et al, 1994). Samples were resuspended in 30 ml SDS ± PAGE loading bu er (60 mM Tris/HCl, pH 6.8, 10% (v/v) glycerol, 3% (w/v) SDS, 5% (v/v) b-mercaptoethanol, 0.005% (w/v) bromphenol blue).…”

Acidic substitution of the activation loop tyrosines in TrkA supports nerve growth factor-independent cell survival and neuronal differentiation

“…While substitution of activation loop residues does not always generate active enzymes (Robbins et al, 1993;Weinmaster and Pawson, 1986;Webster et al, 1996;Ra oni et al, 1998;Alessi et al, 1994), success will depend on understanding how each kinase functions. In this regard, it is clear that there are di erences in the auto-inhibitory mechanisms regulating di erent RTK's.…”