Interleukin-1 activates a novel protein kinase cascade that results in the phosphorylation of hsp27

Signaling by dual specificity kinases

“…Diverse stimuli including in¯ammatory cytokines, osmotic stress, UVirradiation and heat-shock have been shown to activate MKK3 . Activation of MEKK3-p38MAPK signaling pathway leads to the activation of di erent kinases such as MAPKAP-2 (Stokoe et al, 1992;Rouse et al, 1994;Freshney et al, 1994), MAPKAP-3 (Ludwig et al, 1996), and MNK1/2 kinases (Waskiewicz et al, 1997;Fukunaga and Hunter, 1997). Similar to ERKs the phosphorylated p38MAPK translocates to the nucleus and phosphorylates the transcription factors such as ATF2 , CREB (Tan et al, 1996), CHOP (Wang and Ron, 1996), and MEF2C (Han et al, 1997a).…”

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

“…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.…”

“…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].…”

Interleukin 1 activates jun N‐terminal kinases JNK1 and JNK2 but not extracellular regulated MAP kinase (ERK) in human glomerular mesangial cells

“…Abbreviations: IL-I, interleukin 1; TNF, tumor necrosis factor; JNK, jun N-terminal kinase; SAPK, stress-activated protein kinase; PMA, phorbol 12-myristate 13-acetate; bFGF, basic fibroblast growth factor; PDGF, platelet-derived growth factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; M-CSF, macrophage colony-stimulating factor; LPS, lipopolysaccharide; TGF-[3, transforming growth factor [3 1 has been shown to activate various MAP kinases [6][7][8][9][10][11][12]. The aim of the present study was therefore to investigate the regulation of two major MAP kinase pathways, the jun or stressactivated protein kinases and the extracellular regulated kinases, by IL-1 in human mesangial cells.…”