Although classic genetic analyses, such as those described above, have revealed much about the molecular pathways involved in artery-vein specification, such approaches have limitations when it comes to examining signaling pathways that function at multiple stages in development. With a typical nonconditional mutation, the primary role for a gene at later stages of development is often difficult to distinguish from indirect consequences of disrupting the gene at an earlier stage. The Hedgehog pathway, for example, plays a critical role in vasculogenesis, but is also involved in development of numerous other structures at various developmental time points.34 Moreover, classic genetic approaches can be hampered by genetic redundancy.35 A powerful alternative approach, chemical genetic analysis, can overcome the challenges posed by repeated utilization of a signaling pathway during development and by genetic redundancy. Recently, Hedgehog signaling inhibitor cyclopamine was instrumental in ...
MAP kinases are key mediators of cellular differentiation and proliferation in all animals, and they function in receptor tyrosine kinase/Ras signaling pathways (reviewed in Marshall 1994). MAP kinase plays an important role in the Ras signaling pathway because it can activate downstream substrates that directly mediate the cellular response to growth factors, suggesting that MAP kinase acts near or at the end of this signaling pathway (reviewed in Treisman 1996).. MAP kinases are activated when they become phosphorylated by the protein kinase MEK (MAP or ERK kinase; Adams and Parker 1992; Crewset al. 1992b). The major known substrate for MEK is currently MAP kinase, suggesting that the predominant function of MEK may be to activate MAP kinase (Segeret al. 1992). Once activated, a significant fraction of MAP kinase molecules translocate to the nucleus, and many important MAP kinase substrates are localized in the nucleus (e.g., the mammalian transcription factors Elk-1 and Ets-1 (reviewed in ...
Compounds. Compound I [IUPAC name: N-(3-fluoro-4-((7-methoxy-4-quinolinyl)oxy)phenyl)-1-(2-hydroxy-2-methylpropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide] was synthesized at Amgen, Inc. The MAPK/extracellular signal-regulated kinase (ERK) kinase 1/2 (MEK1/2) inhibitor U0126 was obtained from Calbiochem.. Cells. KATOIII (gastric), PC3 (prostate), HT-29 (colorectal), Colo205 (colorectal), BxPC3 (pancreatic), and U-87 MG (glioblastoma) cancer cell lines were obtained from the American Type Culture Collection. NIH3T3 TPR-Met or NIH3T3 RON cells were generated by stable transfection of TPR-Met, a constitutively active, ligand-independent form of c-Met ( 31) or wild-type RON in NIH3T3 cells. Cells were grown as monolayers using standard cell culture conditions.. Antibodies and reagents. Antibodies against c-Met (C-12), RON (C-20), and actin (1615-R) were acquired from Santa Cruz Biotechnology. Antibodies against phospho-c-Met (Y1234/1235), phospho-Gab1 (Y627), phospho-ERK1/2 ...
p42 MAP Kinase (Mitogen-Activated Protein Kinase, MAPK), also known as Erk2 (Extracellular signal-regulated kinase 2) is one of two isoforms of MAP kinase family. It is a serine/threonine protein kinase
Extracellular-signal-regulated kinases (ERKs), also called mitogen-activated protein kinases (MAPKs), are widely expressed signaling proteins that regulate meiosis, mitosis, and postmitotic functions in differentiated cells. Following activation by upstream kinases, ERKs are translocated to the nucleus, where they perform their regulatory functions. Disruption of ERK-mediated pathways is common in many cancers. Two members of this family were originally identified with 85% sequence similarity, called ERK1 and ERK2. ERK1 is also known as MAPK3, extracellular signal-regulated kinase 1, insulin-stimulated MAP2 kinase, microtubule-associated protein 2 kinase, PRKM3, ERT2, p44-ERK1, p44-MAPK, HS44KDAP, HUMKER1A, MAP kinase 1, and MAPK1. ERK2 is also known as MAPK1, extracellular signal-regulated kinase 2, PRKM1, PRKM2, ERT1, p41-ERK1, p41-MAPK, p42-MAPK, MAP kinase 1, MAP kinase 2, MAPK1, MAPK2, p38, p40, and p41.. ...
Extracellular-signal-regulated kinases (ERKs), also called mitogen-activated protein kinases (MAPKs), are widely expressed signaling proteins that regulate meiosis, mitosis, and postmitotic functions in differentiated cells. Following activation by upstream kinases, ERKs are translocated to the nucleus, where they perform their regulatory functions. Disruption of ERK-mediated pathways is common in many cancers. Two members of this family were originally identified with 85% sequence similarity, called ERK1 and ERK2. ERK1 is also known as MAPK3, extracellular signal-regulated kinase 1, insulin-stimulated MAP2 kinase, microtubule-associated protein 2 kinase, PRKM3, ERT2, p44-ERK1, p44-MAPK, HS44KDAP, HUMKER1A, MAP kinase 1, and MAPK1. ERK2 is also known as MAPK1, extracellular signal-regulated kinase 2, PRKM1, PRKM2, ERT1, p41-ERK1, p41-MAPK, p42-MAPK, MAP kinase 1, MAP kinase 2, MAPK1, MAPK2, p38, p40, and p41.. ...
MEK1 is a member of the MAPK signal transduction pathway that responds to growth factors and cytokines. We have determined that the kinase domain spans residue 35 to 382 by proteolytic cleavage. The complete kinase domain has been crystallized and its X-ray crystal structure as a complex with magnesium and ATP-S determined at 2.1 ?. Unlike crystals of a truncated kinase domain previously published, the crystals of the intact domain can be grown either as a binary complex with a nucleotide or a ternary complex with a nucleotide and one of a multitude of allosteric inhibitors. Further the crystals allow for the determination of co-structures with ATP competitive inhibitors. We describe the structures of non-phosphorylated MEK1 (npMEK1) binary complexes with ADP, and K252a, an ATP-competitive inhibitor (see table 1) at 1.9 ?, and 2.7 ? resolution, respectively. Ternary complexes have also been solved between npMEK1, a nucleotide and an allosteric non-ATP competitive inhibitor: ATP-S with ...
The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This protein is a neuronal-specific form of c-Jun N-terminal kinases (JNKs). Through its phosphorylation and nuclear localization, this kinase plays regulatory roles in the signaling pathways during neuronal apoptosis. Beta-arrestin 2, a receptor-regulated MAP kinase scaffold protein, is found to interact with, and stimulate the phosphorylation of this kinase by MAP kinase kinase 4 (MKK4). Cyclin-dependent kinase 5 can phosphorylate, and inhibit the activity of this kinase, which may be important in preventing neuronal apoptosis. Four alternatively spliced transcript variants encoding distinct isoforms have been reported.[3] ...
The p38 MAP kinases are a family of serine/threonine protein kinases that play important roles in cellular responses to external stress signals. Since their identification about 10 years ago, much has been learned of the activation and regulation of the p38 MAP kinase pathways. Inhibitors of two mem …
Figure 2: Examples of the probability distribution (a, b, and c) and trace plots (d, e, and f) of reaction rates 2 (which indicates the simultaneous recruitment of Shc and Grb2-SOS complex from the cytosol to the cell membrane by the recruitment of EGFR (a and d)), 16 (which shows the activation of MEK proteins by active Raf (b and e)), and 38 (which refers to the dissociation of active ERK and RSK complex (c and f)) of Model 2 under ...
PGC-1α-dependent irisin, a novel myokine, is derived from cleaving Fndc5 protein. Irisin promotes brown fat-like development and thermogenesis in WAT both in vitro and in vivo. The discovery of irisin has created an opportunity to further understand the role of adipocytes in obesity, diabetes, and other associated metabolic disorders (12,13,26,27). However, the molecular mechanisms and cellular signaling pathways responsible for the browning effect of irisin have not been elucidated.. In this study, we successfully constructed the yeast expression plasmid containing a synthesized optimal codon usage, human irisin-coding sequence and generated pure human recombinant irisin protein in P. pastoris with high yield that is fully biologically functional. The P. pastoris system is widely used for heterogenic protein expression, with the capacity to generate posttranslational modified proteins (28). The human recombinant irisin protein expressed in yeast showed a predominant band of ∼22 kDa, which is ...
MAPK is involved in the action of most nonnuclear oncogenes. It is responsible for cell response to growth factors such as BDNF or nerve growth factor. Extracellular stimuli lead to activation of a MAP kinase via a signaling cascade ("MAPK cascade") composed of MAP kinase, MAP kinase kinase (MKK or MAP2K), and MAP kinase kinase kinase (MKKK or MAP3K, EC 2.7.11.25). A MAP3K that is activated by extracellular stimuli phosphorylates a MAP2K on its serine and threonine residues, and then this MAP2K activates a MAP kinase through phosphorylation on its serine and tyrosine residues. This MAP kinase signaling cascade has been evolutionarily well-conserved from yeast to mammals. ...
Growth factors and various cellular stresses are known to activate mitogen-activated protein (MAP) kinase, which plays a role in conveying signals from the cytosol to the nucleus. The phosphorylation of MAP kinase is thought to be a prerequisite for translocation. Here, we investigate the translocation and activation of MAP kinase during ischaemia and reperfusion in perfused rat heart. Ischaemia (0-40 min) induces the translocation of MAP kinase from the cytosol fraction to the nuclear fraction. Immunohistochemical observation shows that MAP kinase staining in the nucleus is enhanced after ischaemia for 40 min. Unexpectedly, tyrosine phosphorylation of MAP kinase is unchanged in the nuclear fraction during ischaemia, indicating that unphosphorylated MAP kinase translocates from the cytosol to the nucleus. During reperfusion (0-30 min), after ischaemia for 20 min, tyrosine phosphorylation of MAP kinase in the nuclear fraction is increased with a peak at 10 min of reperfusion. The activation is ...
The MAPK/ERK pathway is a central signaling pathway for many cellular processes, including proliferation, differentiation, and survival. With physiologic signaling, the transcriptional response is coupled to MAPK pathway activation, which is intricately regulated and depends on both the type and duration of upstream stimulus. Negative-feedback regulators of the MAPK pathway, such as the ERK phosphatase DUSP6, are strongly induced to limit the intensity and duration of ERK pathway activation and maintain MAPK signaling homeostasis (11). In cancer, tumors harboring constitutive MAPK/ERK activation express high levels of negative-feedback regulators that are often used as a surrogate biomarker for MAPK/ERK pathway signaling strength, and their rapid decline upon MAPK pathway inhibition indicates therapeutic efficacy, but is also exploited by cancer cells for early adaptation, development of persistent disease, and eventual emergence of resistant disease (11, 39).. The development of potent ...
The protein encoded by this gene is a member of the dual specificity protein kinase family, which acts as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This protein kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon wide variety of extra- and intracellular signals. As an essential component of MAP kinase signal transduction pathway, this kinase is involved in many cellular processes such as proliferation, differentiation, transcription regulation and development ...
Activation of Ras-MAPK signalling pathway is predominantly essential for promoting neuronal cell growth and differentiation. [24]Several pathways derive from Trk receptors for activation of Ras molecules, which begin by formation of ligand-bound mitogen (BDNF or NGF) at an extracellular domain of the trk, causing receptor dimerization. This subsequently will lead to phosphorylation of the intracellular parts of the receptors, which activates Guanine Exchange factors (GEFs), such as sos, Grb2 and Shc. GEFs trigger the exchange of GDP bound to inactive Ras to GTP, resulting Ras to activate. The presence of activated Ras molecules, stimulate signaling via a major downstream pathway known as MAP kinase (mitogen-activated protein kinase)-although activated Ras, would be also capable of triggering several other downstream pathways such as PLC-y1 and PI3-kinases (Figure 3). [24] Mitogen-activated protein kinase (MAPK) pathway involves a series of signalling cascade. Raf is the first component of MAPK, ...
Activation of Ras-MAPK signalling pathway is predominantly essential for promoting neuronal cell growth and differentiation. [19]Several pathways derive from Trk receptors for activation of Ras molecules, which begin by formation of ligand-bound mitogen (BDNF or NGF) at an extracellular domain of the trk, causing receptor dimerization. This subsequently will lead to phosphorylation of the intracellular parts of the receptors, which activates Guanine Exchange factors (GEFs), such as sos, Grb2 and Shc. GEFs trigger the exchange of GDP bound to inactive Ras to GTP, resulting Ras to activate. The presence of activated Ras molecules, stimulate signaling via a major downstream pathway known as MAP kinase (mitogen-activated protein kinase)-although activated Ras, would be also capable of triggering several other downstream pathways such as PLC-y1 and PI3-kinases (Figure..). [19] Mitogen-activated protein kinase (MAPK) pathway involves a series of signalling cascade. Raf is the first component of MAPK, ...
ALK_HUMAN] Neuronal orphan receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system. Transduces signals from ligands at the cell surface, through specific activation of the mitogen-activated protein kinase (MAPK) pathway. Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif. Following activation by ligand, ALK induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Acts as a receptor for ligands pleiotrophin (PTN), a secreted growth factor, and midkine (MDK), a PTN-related factor, thus participating in PTN and MDK signal transduction. PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation. MDK-binding induces phosphorylation of the ALK target insulin receptor ...
MAPK3 [ENSP00000263025]. Extracellular signal-regulated kinase 1; Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are ...
MAPKs function as the terminal components of three-tiered cascades of kinases comprised of a MAPK kinase kinase (MAP3K), MAPK kinase (MAP2K), and MAPK and are important signal transducers in development, homeostasis, and disease (Chang and Karin, 2001). For example, the p38 subfamily of MAPKs is involved in a wide variety of biological processes, including inflammation, stress responses, and cell differentiation (Zarubin and Han, 2005). The myriad roles of MAPK cascades indicate that the specificity of MAPK activation and function must be regulated. One mechanism by which this occurs is via MAPK scaffold proteins, which are thought to provide (1) specificity between distinct MAPK subfamilies by assembling individual MAPK modules and (2) precise spatial and temporal regulation to MAPK signaling (Morrison and Davis, 2003). How this latter function is accomplished is unclear, but it suggests that scaffold proteins may interact with cell-type specific factors.. Differentiation of cells in the ...
A series of 3-(4-fluorophenyl)-2-(4-pyridyl)-chromone derivs. were synthesized and evaluated as p38 MAP kinase inhibitors. Introduction of an amino group in the 2-position of the pyridyl moiety gave p38 inhibitors with IC50 values in the low nanomolar range (e.g. 8a; IC50 = 17 nm). Addnl., the inhibitors (8a and 8e) demonstrate an excellent selectivity profile towards the p38 kinase among other kinases, as well as inhibition (8e) of p38 signaling in human breast cancer cells. [on SciFinder(R)]. ...
ASK1, 0.1 ml. Mitogen-activated protein kinase (MAPK) signaling cascades include MAPK or extracellular signal-regulated kinase (ERK), MAPK kinase (MKK or MEK), and MAPK kinase kinase (MAPKKK or MEKK).
Pre-mRNA splicing occurs in two sequential transesterification steps, and the protein encoded by this gene is thought to be involved in pre-mRNA splicing and in signal transduction. This protein belongs to a kinase family that includes serine/arginine-rich protein-specific kinases and cyclin-dependent kinases (CDKs). This protein is regarded as a CDK-like kinase (Clk) with homology to mitogen-activated protein kinases (MAPKs). [provided by RefSeq, Jul 2008 ...
Contact Us. Tel:732-484-9848. Fax:888-484-5008. Email:[email protected]. Add:1 Deer Park Dr, Suite Q,. Monmouth Junction, NJ 08852, USA. ...
The protein encoded by this gene is a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act in a signaling cascade that regulates various cellular processes such as proliferation, differentiation, and cell cycle progression in response to a variety of extracellular signals. This kinase is activated by upstream kinases, resulting in its translocation to the nucleus where it phosphorylates nuclear targets. Alternatively spliced transcript variants encoding different protein isoforms have been described. [provided by RefSeq, Jul 2008 ...
Easy-to-use kits for performing kinase selectivity profiling that rely on the ADP-Glo Kinase Assay technology. Each system includes kinase and substrate pairs in an easy-to-use 8-tube strip format optimized for fast and simple kinase profiling reactions.
Lately, Caldwell and co-workers (2006) offered a systemic review and meta-analysis of double-blind, randomized, managed research of celecoxib to measure the threat of cardiovascular occasions. Read More. ...
Supplementary MaterialsText S1: Supplementary materials and strategies(0. DOC) pone.0006162.s009.doc (51K) GUID:?0E3CC820-5208-4049-BD38-17C589D75924 Desk S8: Assessment of CV between nERGs and tERGs in the dataset(0.04 MB DOC) Read More ...
ERK1 / ERK2, 0.1 ml. Erk1 and Erk2 are closely related mitogen activated protein (MAP) kinases which are activated by many growth factors, mitogens and differentiation-promoting agents via a protein kinase cascade.
PI 3 Kinase p85 alpha + Gamma兔多克隆抗体(ab74136)可与小鼠, 大鼠, 人样本反应并经WB, ELISA, IHC, ICC/IF实验严格验证,被3篇文献引用并得到2个独立的用户反馈。
If you know of any papers that use this antibody, please contact us at antibodies [at] alzforum [dot] org for consideration in the References section.. ...
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高い抗原親和性、特異性と安定した品質を兼ね備えたアブカムのウサギ・モノクローナル抗体 RabMAb® ab79422 交差種: Hu 適用: WB
Unknown functionEnzymes of unknown specificitylipid kinase, YegS/Rv2252/BmrU family (TIGR00147; EC 2.7.1.-; HMM-score: 307.9) ...
MetabolismBiosynthesis of cofactors, prosthetic groups, and carriersThiaminethiamine kinase (TIGR02721; EC 2.7.1.89; HMM-score: 32.1) ...
The p38 mitogen-activated protein (MAP) kinase signal transduction pathway is activated by proinflammatory cytokines and environmental stress. The detection of p38 MAP kinase in the nucleus of activated cells suggests that p38 MAP kinase can mediate signaling to the nucleus. To test this hypothesis, we constructed expression vectors for activated MKK3 and MKK6, two MAP kinase kinases that phosphorylate and activate p38 MAP kinase. Expression of activated MKK3 and MKK6 in cultured cells caused a selective increase in p38 MAP kinase activity. Cotransfection experiments demonstrated that p38 MAP kinase activation causes increased reporter gene expression mediated by the transcription factors ATF2 and Elk-1. These data demonstrate that the nucleus is one target of the p38 MAP kinase signal transduction pathway. ...
Raingeaud J., Whitmarsh A.J., Barrett T., Derijard B., Davis R.J.. The p38 mitogen-activated protein (MAP) kinase signal transduction pathway is activated by proinflammatory cytokines and environmental stress. The detection of p38 MAP kinase in the nucleus of activated cells suggests that p38 MAP kinase can mediate signaling to the nucleus. To test this hypothesis, we constructed expression vectors for activated MKK3 and MKK6, two MAP kinase kinases that phosphorylate and activate p38 MAP kinase. Expression of activated MKK3 and MKK6 in cultured cells caused a selective increase in p38 MAP kinase activity. Cotransfection experiments demonstrated that p38 MAP kinase activation causes increased reporter gene expression mediated by the transcription factors ATF2 and Elk-1. These data demonstrate that the nucleus is one target of the p38 MAP kinase signal transduction pathway.. Mol. Cell. Biol. 16:1247-1255(1996) [PubMed] [Europe PMC] ...
We have previously reported the in vitro pharmacological properties of E6201, including the following: 1) E6201 suppressed the activation of AP-1 via inhibitory effects on mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-1 and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase-; 2) E6201 decreased activation of NF-κB; 3) E6201 suppressed the production of various proinflammatory cytokines in human monocytes and leukocytes; and 4) E6201 attenuated hyperproliferation and IL-8 production in human keratinocytes in vitro (Goto et al., 2009). These pharmacological properties of E6201 indicate that this compound represents a promising strategy for the treatment of psoriasis, because psoriasis is a chronic inflammatory skin disease characterized by severe hyperplasia in the epidermis and marked infiltration of leukocytes into dermis and epidermis. In this article, we investigated the therapeutic effects of topically administered E6201 in ...
TY - JOUR. T1 - The Mechanism of Heat Shock Activation of ERK Mitogen-activated Protein Kinases in the Interleukin 3-dependent ProB Cell Line BaF3. AU - Ng, D.C.H.. AU - Bogoyevitch, M.A.. PY - 2000. Y1 - 2000. M3 - Article. VL - 275. SP - 40856. EP - 40866. JO - The Journal of Biological Chemistry. JF - The Journal of Biological Chemistry. SN - 0021-9258. IS - 52. ER - ...
Kaur R., Liu X., Gjoerup O., Zhang A., Yuan X., Balk S.P., Schneider M.C., Lu M.L.. The p21-activated kinases (PAKs) contain an N-terminal Cdc42/Rac interactive binding domain, which in the group 1 PAKs (PAK1, 2, and 3) regulates the activity of an adjacent conserved autoinhibitory domain. In contrast, the group 2 PAKs (PAK4, 5, and 6) lack this autoinhibitory domain and are not activated by Cdc42/Rac binding, and the mechanisms that regulate their kinase activity have been unclear. This study found that basal PAK6 kinase activity was repressed by a p38 mitogen-activated protein (MAP) kinase antagonist and could be strongly stimulated by constitutively active MAP kinase kinase 6 (MKK6), an upstream activator of p38 MAP kinases. Mutation of a consensus p38 MAP kinase target site at serine 165 decreased PAK6 kinase activity. Moreover, PAK6 was directly activated by MKK6, and mutation of tyrosine 566 in a consensus MKK6 site (threonine-proline-tyrosine, TPY) in the activation loop of the PAK6 ...
TY - JOUR. T1 - Lithium protection of phencyclidine-induced neurotoxicity in developing brain. T2 - The role of phosphatidylinositol-3 kinase/Akt and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling pathways. AU - Xia, Yan. AU - Wang, Cheng Z.. AU - Liu, Jie. AU - Anastasio, Noelle. AU - Johnson, Kenneth M.. PY - 2008/9. Y1 - 2008/9. N2 - Phencyclidine (PCP) and other N-methyl-D-aspartate (NMDA) receptor antagonists have been shown to be neurotoxic to developing brains and to result in schizophrenia-like behaviors later in development. Prevention of both effects by antischizophrenic drugs suggests the validity of PCP neurodevelopmental toxicity as a heuristic model of schizophrenia. Lithium is used for the treatment of bipolar and schizoaffective disorders and has recently been shown to have neuroprotective properties. The present study used organotypic corticostriatal slices taken from postnatal day 2 rat pups to investigate the protective effect of ...
Three-tiered kinase modules, such as the Raf-MEK (mitogen-activated or extracellular signal-regulated protein kinase kinase)-ERK (extracellular signal-regulated kinase) mitogen-activated protein kinase pathway, are widespread in biology, suggesting that this structure conveys evolutionarily advantageous properties. We show that the three-tiered kinase amplifier module combined with negative feedback recapitulates the design principles of a negative feedback amplifier (NFA), which is used in electronic circuits to confer robustness, output stabilization, and linearization of nonlinear signal amplification. We used mathematical modeling and experimental validation to demonstrate that the ERK pathway has properties of an NFA that (i) converts intrinsic switch-like activation kinetics into graded linear responses, (ii) conveys robustness to changes in rates of reactions within the NFA module, and (iii) stabilizes outputs in response to drug-induced perturbations of the amplifier. These properties ...
This study uncovered a function of the dual specificity ERK MAP kinase phosphatase, MKP3, for the specification of mesenchymal progenitors in the somite sclerotome. We showed that Mkp3 was expressed in a twin-striped pattern, which closely matched the emergence of scleraxis transcripts along the anteroposterior somite edges (Fig. 1). This pattern suggested a link between the modulation of FGF signalling by MKP3 and scleraxis expression. We demonstrated that somitic expression of Mkp3 in the dorsal sclerotome was itself dependent on active ERK MAP kinase. This implied that FGF signalling in dorsal sclerotome cells is modulated by a negative feedback loop, which involves MKP3 and ERK MAP kinase. Indeed, we found that the levels of Mkp3 transcripts detected in response to FGF beads can cycle between extensive overexpression after a short exposure to complete loss of endogenous Mkp3 message after 24 hours (Fig. 3A-C; data not shown). We showed by western blot analysis that this dynamic response ...
MAPK signaling cascades seem to play divergent roles in the prostate gland. Significant differences have been observed in the activation pattern of all MAPK network components in prostate epithelial and stromal cells, under normal and pathologic conditions. Modulation of MAPK pathways has been shown in several prostate cancer cell lines by growth factors, cytokines, and a variety of agents that control growth and apoptosis of prostate cancer cells. However, structure and function of MAPK signal transduction pathways have not been thoroughly defined in prostate carcinogenesis.. The prostate is a heterogeneous gland comprising several cell types, which regulate each others function by paracrine mechanisms. Hence, it is important to decipher the role played by MAPK signal transduction pathways in mediating the interaction between various neighboring prostate cell types. A diverse array of signaling cascades have been identified as activating elements upstream of the MAPK circuitry. In-depth ...
TY - JOUR. T1 - Cell-cycle control linked to extracellular environment by MAP kinase pathway in fission yeast. AU - Shiozaki, Kazuhiro. AU - Russell, Paul. PY - 1995/12/14. Y1 - 1995/12/14. N2 - In fission yeast the onset of mitosis is brought about by Cdc2/Cdc13 kinase, which is inhibited by the Wee1/Mik1 tyrosine kinases and activated by Cdc25 tyrosine phosphatase. This control network integrates many signals, including those that monitor DNA replication, DNA damage and cell size. We report here that a fission yeast MAP kinase pathway links the cell-cycle G2/M control with changes in the extracellular environment that affect cell physiology. Fission yeast spc1- mutants have a G2 delay that is greatly exacerbated by growth in high osmolarity media and nutrient limitation. A lethal interaction of spc1 and cdc25 mutations shows that Spc1 promotes the onset of mitosis. Spc1 is a MAP kinase homologue that is activated by Wis1 kinase in response to osmotic stress and nutrient limitation. Spc1 is ...
Investigation of T-helper type 2 cytokines and the mitogen-activated protein kinase pathway in the modulation of bronchial hyperresponsiveness, airway inflammation and remodelling ...
The Arabidopsis thaliana genome contains genes encoding 10 MAP kinase kinase (MKK) and 20 Map kinase (MAPK) proteins, however the exact relationship between upstream MKK activators and downstream MAPK protein partners has not fully elucidated. In this study, the yeast two -hybrid system was used to identify protein-protein interactions between all Arabidopsis MAPKs and MKKs. In the yeast two- hybrid assay, the result from the qualitative β-galactosidase filter assay showed that 6 MAPK proteins interacted with 6 MKK proteins. Quantitative β-galactosidase liquid assay was used to confirm the interactions between MAPK and MKK in yeast. The BiFC approach was used to test whether MKK1, MKK2 and MKK6 associated with MPK4 and MPK11 in vivo in Arabidopsis. In these assays, GFP fluorescence was observed in the protoplasts suggesting that MKK1, MKK2 and MKK6 interact with MPK4 and MPK11, respectively. However, evidence of reciprocal interaction was only seen with the combination of MKK1 and MPK11, and ...
Purification and characterization of two isoenzymes of DL-glycerol-3-phosphatase from Saccharomyces cerevisiae. Identification of the corresponding GPP1 and GPP2 genes and evidence for osmotic regulation of Gpp2p expression by the osmosensing mitogen-activated protein kinase signal transduction pathway ...
au08-06_mpk6_heat_stressed - au08-06_mpk6_heat_stressed - Mitogen Activated Protein Kinase (MAPK) signaling pathways are key regulators of cell proliferation, differentiation and stress effectors. The core of the MAP kinase signal transduction cascade is composed of a three-kinase module consisting of a MAP kinase kinase kinase (MAPKKK), a MAP kinase kinase (MAPKK), and a MAP kinase (MAPK). The signaling pathway is activated upon stimulation by a phosphorylation cascade. In previous studies, it was shown that the mpk6 KO mutant plants are significantly more tolerant to heat stress in comparison to wt and that after 3h treatment at 37°C, an activation of heat-shock proteins occures in the mpk6 mutant. To better understand the changes occuring in the mpk6 mutant upon heat stress at the gene expression level, we would like to perform a microarray transcriptomic analysis. - Mitogen Activated Protein Kinase (MAPK) signaling pathways are key regulators of cell proliferation, differentiation and stress