A novel kinase cascade triggered by stress and heat shock that stimulates MAPKAP kinase-2 and phosphorylation of the small heat shock proteins

Rouse, John; Cohen, Philip; Trigon, Sylviane; Morange, Michel; Alonso‐Llamazares, Ana; Zamanillo, Daniel; Hunt, Tim; Nebreda, Ángel R.

doi:10.1016/0092-8674(94)90277-1

Cited by 1,601 publications

(1,276 citation statements)

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“…The p38 MAPK is activated by MKK3/ 6, and by MKK4 (also activates JNKs, known to be stimulated by HRG, ). Activated p38 MAPK phosphorylates and activates MAPK activated protein kinase-2 (MAPKAPK-2) (Rouse et al, 1994), mitogen-and stress-activated protein kinase-1 (MSK1) (Deak et al, 1998), and the transcription factors ATF2, Max and CREB.…”

Section: Discussionmentioning

confidence: 99%

Serine phosphorylation of paxillin by heregulin-β1: role of p38 mitogen activated protein kinase

et al. 1999

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The mechanisms through which heregulin (HRG) regulates the progression of breast cancer cells to a more invasive phenotype are currently unknown. Recently we have shown that HRG treatment of breast cancer cells leads to the formation of lamellipodia/ ®lopodia, and increased cell migration and invasiveness through the phosphatidylinositol 3-kinase (PI-3 kinase).Since the process of cell migration must involve changes in adhesion, we explored the potential HRG regulation of paxillin, a major cytoskeletal phosphoprotein of focal adhesion. We report that HRG stimulation of noninvasive breast cancer cells resulted in stimulation of p38 mitogen-activated protein kinase (p38 MAPK ), extracellular signal-regulated kinases (ERK) and PI-3K, and a concurrent unexpected increase in the level of paxillin phosphorylation on serine residue which was sensitive to protein-phosphatase 2b but not to protein tyrosine phosphatase 1. In addition, HRG triggered a rapid redistribution of paxillin to the perinuclear regions from the tyrosine-phosphorylated focal adhesions, and increased cell scattering. There was no e ect of HRG on the state of phosphorylation and localization of focal adhesion kinase. The HRG-induced increase in serine phosphorylation of paxillin and cell scattering were selectively inhibited by a speci®c inhibitor of p38 MAPK or a dominant-negative p38 MAPK mutant, but not by inhibitors of p42/44 MAPK or PI-3 kinase pathways. For the ®rst time our results have shown that HRG, a potent migratory growth factor stimulates serine phosphorylation of paxillin. These ®ndings suggest a role of p38 MAPKdependent signal transduction pathway(s) in serine phosphorylation and disassembly of the paxillin from the focal complexes during HRG-induced cell shape alterations and motility.

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Section: Discussionmentioning

confidence: 99%

Serine phosphorylation of paxillin by heregulin-β1: role of p38 mitogen activated protein kinase

et al. 1999

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“…This preparation also migrates as two bands with apparent molecular masses of 65 and 62 kDa. Each enzyme was activated by incubation with the Xenopus homologue of SAPK-2 [11] which had been expressed in E. coli [5] and then activated by the MAP kinase kinase homologue MKK6 from skeletal muscle [20]. Only the 65 kDa band of MAPKAP-K2 [11] and the 67 kDa band of MAPKAP-K3 are phosphorylated by SAPK-2.…”

Section: Methodsmentioning

confidence: 99%

“…KB [4] and HeLa [5] cells were cultured as described previously, incubated for 1 h with or without 10 ~tM SB 203580, then exposed to either chemical (0.5 mM sodium arsenite) or osmotic (0.5 M sorbitol) stress, or stimulated with IL-1 (20 ng/ml), TNFc~ (100 ng/ml) or anisomycin (10 Izg/ml) for the times indicated in the figures. Each 6 cm dish of cells was lysed in 0.2 ml of buffer as described [5], except that 2 BM microcystin was also present in the lysis buffer.…”

Section: Cell Culture Stimulation and Lysismentioning

confidence: 99%

“…Each 6 cm dish of cells was lysed in 0.2 ml of buffer as described [5], except that 2 BM microcystin was also present in the lysis buffer.…”

Section: Cell Culture Stimulation and Lysismentioning

confidence: 99%

“…In vivo, however, MAPKAP-K2 is activated by a distinct MAP kinase homologue termed stress-activated protein kinase-2 (SAPK-2), also known as p38 [3], p40 [4], RK [5], CSBP [6] and Mxi2 [7]. SAPK-2 and MAPKAP-K2 become activated within a few minutes when cells are stimulated with the cytokines interleukin-1 (IL-1) [4] or tumour necrosis factor (TNF) [8], with bacterial lipopolysaccharide (LPS) [6,9] or when stressed in a variety of ways, for example by exposure to heat or osmotic shock, UV irradiation, sodium arsenite or anisomycin [3,5,10]. The activation of MAPKAP-K2 by these stimuli is prevented if cells are first incubated with SB 203580, a specific inhibitor of SAPK-2 which does not affect the activity or activation of other MAP kinase family members, such as p42/p44 MAP kinases or SAPK-1 (also termed JNK) [9].…”

Section: Introductionmentioning

confidence: 99%

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A comparison of the substrate specificity of MAPKAP kinase‐2 and MAPKAP kinase‐3 and their activation by cytokines and cellular stress

1996

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MAPKAP kinase-2 and MAPKAP kinase-3 were both activated in response to cellular stress, interleukin-1 and tumour necrosis factor in KB and HeLa cells, and with identical kinetics. Activation of MAPKAP kinase-3, like MAPKAP kinase-2, was prevented by SB 203580, a specific inhibitor of SAPK-2, the upstream activator of MAPKAP kinase-2. MAPKAP kinase-3 and MAPKAP kinase-2 pbospborylated peptide substrates with similar kinetic constants and phospborylated the same serine residues in HSP27 at the same relative rates. These results establish that MAPKAP kinase-3 lies 'downstream' of SAPK-2 and that it is likely to have overlapping or identical substrates to MAPKAP kinase-2 in vivo.

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Isolation and sequence of theHOG1 homologue fromDebaryomyces hansenii by complementation of thehog1? strain ofSaccharomyces cerevisiae

Bansal

Mondal

2000

Yeast

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A novel kinase cascade triggered by stress and heat shock that stimulates MAPKAP kinase-2 and phosphorylation of the small heat shock proteins

Cited by 1,601 publications

References 55 publications

Serine phosphorylation of paxillin by heregulin-β1: role of p38 mitogen activated protein kinase

Serine phosphorylation of paxillin by heregulin-β1: role of p38 mitogen activated protein kinase

A comparison of the substrate specificity of MAPKAP kinase‐2 and MAPKAP kinase‐3 and their activation by cytokines and cellular stress

Isolation and sequence of theHOG1 homologue fromDebaryomyces hansenii by complementation of thehog1? strain ofSaccharomyces cerevisiae

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