Browsing by Subject "MAP kinase"
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- PublicationRestrictedActivation of the cell integrity pathway is channelled through diverse signalling elements in fission yeast(ELSEVIER, 2008-01-04) Barba, Gregorio; Soto, Teresa; Madrid, Marisa; Núñez, Andrés; Vicente, Jero; Gacto, Mariano; Cansado Vizoso, José; Genética y MicrobiologíaMAPK Pmk1p is the central element of a cascade involved in the maintenance of cell integrity and other functions in Schizosaccharomyces pombe. Pmk1p becomes activated by multiple stressing situations and also during cell separation. GTPase Rho2p acts upstream of the protein kinase C homolog Pck2p to activate the Pmk1 signalling pathway through direct interaction with MAPKKK Mkh1p. In this work we analyzed the functional significance of both Rho2p and Pck2p in the transduction of various stress signals by the cell integrity pathway. The results indicate that basal Pmk1p activity can be positively regulated by alternative mechanisms which are independent on the control by Rho2p and/or Pck2p. Unexpectedly, Pck1p, another protein kinase C homolog, negatively modulates Pmk1p basal activity by an unknown mechanism. Moreover, different elements appear to regulate the stress-induced activation of Pmk1p depending on the nature of the triggering stimuli. Whereas Pmk1p activation induced by hyper- or hypotonic stresses is channeled through Rho2p–Pck2p, other stressors, like glucose deprivation or cell wall disturbance, are transduced via other pathways in addition to that of Rho2p–Pck2p. On the contrary, Pmk1p activation observed during cell separation or after treatment with hydrogen peroxide does not involve Rho2p–Pck2p. Finally, Pck2p function is critical to maintain a Pmk1p basal activity that allows Pmk1p activation induced by heat stress. These data demonstrate the existence of a complex signalling network modulating Pmk1p activation in response to a variety of stresses in fission yeast.
- PublicationOpen AccesscAMP-Protein Kinase A and Stress-Activated MAP Kinase 1 signaling mediate transcriptional control of autophagy in fission yeast during glucose limitation or starvation.(Taylor and Francis Group, 2022-09-26) Pérez Díaz, Armando Jesús; Vázquez Marín, Beatriz; Vicente Soler, Jero; Prieto Ruiz, Francisco; Soto, Teresa; Franco, Alejandro; Cansado Vizoso, José; Madrid, Marisa; Genética y MicrobiologíaMacroautophagy/autophagy is an essential adaptive physiological response in eukaryotes induced during nutrient starvation, including glucose, the primary immediate carbon and energy source for most cells. Although the molecular mechanisms that induce autophagy during glucose starvation have been extensively explored in the budding yeast Saccharomyces cerevisiae, little is known about how this coping response is regulated in the evolutionary distant fission yeast Schizosaccharomyces pombe. Here, we show that S. pombe autophagy in response to glucose limitation relies on mitochondrial respiration and the electron transport chain (ETC), but, in contrast to S. cerevisiae, the AMP-activated protein kinase (AMPK) and DNA damage response pathway components do not modulate fission yeast autophagic flux under these conditions. In the presence of glucose, the cAMP-protein kinase A (PKA) signaling pathway constitutively represses S. pombe autophagy by downregulating the transcription factor Rst2, which promotes the expression of respiratory genes required for autophagy induction under limited glucose availability. Furthermore, the stress-activated protein kinase (SAPK) signaling pathway, and its central mitogen-activated protein kinase (MAPK) Sty1, positively modulate autophagy upon glucose limitation at the transcriptional level through its downstream effector Atf1 and by direct in vivo phosphorylation of Rst2 at S292. Thus, our data indicate that the signaling pathways that govern autophagy during glucose shortage or starvation have evolved differently in S. pombe and uncover the existence of sophisticated and multifaceted mechanisms that control this self-preservation and survival response.
- PublicationOpen AccessLow density lipoproteins and mitogenic signal transduction processes: Role in the pathogenesis of renal disease(Murcia : F. Hernández, 2002) Kamanna, V.S.Abnormalities in lipid and lipoprotein metabolism are commonly observed in patients with chronic renal disease. Specifi c a l l y, hyperlipidemia and the glomerular deposition of atherogenic lipoproteins (e.g., Low density lipoprotein, LDL; and its oxidized variants) are implicated in key pathobiological processes i nvo l ved in the development of glomerular disease, including stimulation of monocyte infiltration into the mesangial space, mesangial cell hy p e r c e l l u l a r i t y, and mesangial extracellular matrix deposition. This rev i ew discusses recent understanding of glomerular mitogenic responses, intracellular signaling events associated with mesangial hypercellularity in renal diseases, and the participation of cholesterol and atherogenic lipoproteins in intracellular signaling pathways involved in mesangial cell proliferation. G e n e r a l l y, the mitogenic intracellular signaling p a t h ways are regulated by the activation of series of transmembrane and cytoplasmic protein tyrosine kinases that converge into the activation of Ras and down-stream m i t o g e n - a c t ivated protein kinase (MAP kinase). A c t ivated MAP kinase, through translocating into the nucleus and the activation of various transcription factors and protooncogenes, regulate cell proliferation. The importance of mitogenic intracellular signaling in mesangial proliferative disease has only recently been recognized and showed that the activation of MAP kinase and/or cy c l i n / cyclin-dependent kinases play crucial role in different phases of cell growth cycle and hypercellularity of glomerular cells in va r i o u s experimental renal diseases. Using glomerular mesangial cells as an in-vitro model system, studies from our laboratory indicated that the accumulation of LDL and more potently its oxidized forms within the glomerulus, through the activation of membrane receptor tyrosine kinases (e.g., EGF receptor), activate Ras and MAP kinase signaling cascade leading to DNA synthesis and subsequent mesangial cell proliferation. These data suggest that atherogenic lipoproteins may act as one of the major endogenous modulators for mitogenic signaling response and cell proliferation within the glomerulus. It is reasonable to speculate that the correction or reduction of hy p e r l i p i d e m i a , glomerular lipid deposition, and the pro-oxidative milieu within the glomerulus, through the inhibition of mitogenic signaling events, may provide protective e nvironment against mesangial hypercellularity and subsequent matrix deposition, and the progression of renal disease.
- PublicationOpen AccessMolecular roles of MAP kinases and FADD phosphorylation in prostate cancer(Murcia : F. Hernández, 2006) Shimada, K.; Nakamura, M.; Ishida, E.; Konishi, N.Mitogen activated protein (MAP) kinases are well known serine threonine kinases that modulate gene expression, mitosis, cell proliferation and programmed cell death or ‘apoptosis’ in response to various stresses. Extracellular stress regulated kinase (ERK), c-jun NH2 terminal kinase and p38 are major members of the MAP kinases, and there is now a body of evidence of their involvement in genesis or sensitivity to chemotherapy of human prostate cancers. In this review, we focus on the molecular roles of MAP kinases and their pathological correlations, with particular attention to novel downstream signals through phosphorylation of the Fasassociated death domain protein that effectively regulates not only apoptosis but also the cell cycle in prostate neoplastic cells.
- PublicationOpen AccessProsaposin expression in the regenerated muscles of mdx and cardiotoxin-treated mice(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2013) Li, Cheng; Gao, Hui-ling; Shimokawa, Tetsuya; Nabeka, Hiroaki; Hamada, Fumihiko; Araki, Hiroaki; Cao, Ya-ming; Kobayashi, Naoto; Matsuda, SeijiThe trophic factor prosaposin (PS) is strongly expressed in skeletal muscle, and reportedly, a PS-derived peptide attenuates loss of muscle mass after nerve injury in vivo and increases myoblast fusion into myotubes in vitro. However, few studies have focused on the role of PS during muscle regeneration. We examined the expression of PS in the skeletal muscles in normal, mdx, and cardiotoxin (CTX)-treated mice using immunofluorescence staining, Western blotting, and in situ hybridisation. Immunofluorescence showed intense PS immunoreactivity in the peripheral cytoplasm of uninjured myofibres of normal mice and regenerated myofibres of 8 weeks post-CTX-injection mice. In early stage CTX-treated mice (14 days and earlier), intense PS immunoreactivity was also detected in the immune cells that infiltrated damaged muscle, but it was weak for regenerating myofibres. Western blot confirmed these findings. In contrast, PS was continuously low in mdx mice in both immunofluorescence and Western blotting. In situ hybridisation confirmed the decrease of PS mRNA in regenerated myofibres and revealed the main form of PS mRNA as Pro+0 without a 9-base insertion both in normal and mdx mice. The embryonic myosin (MYH3) was clearly localized in the newly regenerated myofibres at 3, 7, and 14 days of post-CTX-injection and mdx mice, but was lower in the late stage of regenerated myofibres (28 and 56 days post-CTX injection). The inverse distribution of MYH3 and PS indicates that the PS expression is closely related to the differentiation of regenerated myofibres. Investigation of the mitogen-activated protein (MAP) kinase signal pathway showed the inversely synchronous correlation of phosphorylated ERK1/2 with myofibre PS and the synchronous correlation of phosphorylated p-38 with myofibre PS. These data suggest that PS is involved in the regulation of muscle differentiation of regenerated fibres.
- PublicationOpen AccessStress-activated MAPK signaling controls fission yeast actomyosin ring integrity by modulating formin For3 levels(ELIFE SCIENCES PUBLICATIONS LTD, 2020-09-11) Gómez-Gil, E.; Martín-García, R.; Vicente-Soler, J.; Franco, A.; Vázquez-Marín, B.; Prieto-Ruiz, F.; Soto, T.; Pérez, P.; Madrid, M.; Cansado Vizoso, José; Genética y MicrobiologíaCytokinesis, which enables the physical separation of daughter cells once mitosis has been completed, is executed in fungal and animal cells by a contractile actin- and myosin-based ring (CAR). In the fission yeast Schizosaccharomyces pombe, the formin For3 nucleates actin cables and also co-operates for CAR assembly during cytokinesis. Mitogen-activated protein kinases (MAPKs) regulate essential adaptive responses in eukaryotic organisms to environmental changes. We show that the stress-activated protein kinase pathway (SAPK) and its effector, MAPK Sty1, downregulates CAR assembly in S. pombe when its integrity becomes compromised during cytoskeletal damage and stress by reducing For3 levels. Accurate control of For3 levels by the SAPK pathway may thus represent a novel regulatory mechanism of cytokinesis outcome in response to environmental cues. Conversely, SAPK signaling favors CAR assembly and integrity in its close relative Schizosaccharomyces japonicus, revealing a remarkable evolutionary divergence of this response within the fission yeast clade.
- PublicationOpen AccessStress-activated protein kinase-mediated down-regulation of the cell integrity pathway mitogen-activated protein kinase Pmk1p by protein phosphatases(American Society for Cell Biology, 2007-08-29) Madrid, Marisa; Núñez, Andrés; Soto, Teresa; Vicente, Jero; Gacto, Mariano; Cansado Vizoso, José; Genética y MicrobiologíaFission yeast mitogen-activated protein kinase (MAPK) Pmk1p is involved in morphogenesis, cytokinesis, and ion homeostasis as part of the cell integrity pathway, and it becomes activated under multiple stresses, including hyper- or hypotonic conditions, glucose deprivation, cell wall-damaging compounds, and oxidative stress. The only protein phosphatase known to dephosphorylate and inactivate Pmk1p is Pmp1p. We show here that the stress-activated protein kinase (SAPK) pathway and its main effector, Sty1p MAPK, are essential for proper deactivation of Pmk1p under hypertonic stress in a process regulated by Atf1p transcription factor. We demonstrate that tyrosine phosphatases Pyp1p and Pyp2p, and serine/threonine phosphatase Ptc1p, that negatively regulate Sty1p activity and whose expression is dependent on Sty1p-Atf1p function, are involved in Pmk1p dephosphorylation under osmostress. Pyp1p and Ptc1p, in addition to Pmp1p, also control the basal level of MAPK Pmk1p activity in growing cells and associate with, and dephosphorylate Pmk1p both in vitro and in vivo. Our results with Ptc1p provide the first biochemical evidence for a PP2C-type phosphatase acting on more than one MAPK in yeast cells. Importantly, the SAPK-dependent down-regulation of Pmk1p through Pyp1p, Pyp2p, and Ptc1p was not complete, and Pyp1p and Ptc1p phosphatases are able to negatively regulate MAPK Pmk1p activity by an alternative regulatory mechanism. Our data also indicate that Pmk1p phosphorylation oscillates as a function of the cell cycle, peaking at cell separation during cytokinesis, and that Pmp1p phosphatase plays a main role in regulating this process.