Erk Kerinci

Erk Kerinci. Sustained ERK activation is a prominent abnormality in a large number of cancers In addition to upstream signaling cascades ERK is constitutively activated by genetic events such mutation of BRAF kinase an aberration most frequently observed in colorectal cancer and malignant melanoma (Davies et al 2002 Hodis et al 2012).

IntroductionMAPK Signalling PathwaysERK/MAPK Structure and FunctionsActivation of The ERK/MAPK SignallingpathwayDownstream of ERK1/2ConclusionsFundingAuthors&#39 ContributionsExtracellular signalregulated kinase 1/2 (ERK)belongs to the mitogenactivated protein kinase (MAPK) familywhich plays a role in signalling cascades and transmitsextracellular signals to intracellular targets Therefore MAPKcascades are central signalling elements that regulate basicprocesses including cell proliferation differentiation and stressresponses (1–3) These cascades transmit signals throughsequential activation of three to five layers of protein kinasesknown as MAPK kinase kinase kinase (MAP4K) MAPK kinase kinase(MAP3K) MAPK kinase (MAPKK) MAPK and MAPKactivated proteinkinases (MAPKAPK) The first three central layers are considered asa basic core unit while the last two layers appear in somecascades and can vary among cells and stimuli Four MAPK cascadeshave been defined based on the components in the MAPK layerERK1/2 cJun Nterminal kinase (JNK) p38 MAPK and ERK5 Thisreview focuses on the ERK cascade (4–6) whichinvolves several kinases in the MAP3K layer Among the numerous intracellular signallingpathways the MAPK pathway plays a more important role in cellproliferation differentiation apoptosis angiogenesis and tumourmetastasis than other pathways The following four MAPK cascadeshave been identified in eukaryotic cells ERK JNK/stressactivatedprotein kinase p38 MAPK and ERK5 signal transduction pathwaysEach MAPK signalling cascade consists of at least three tiersMAP3K MAPKK and MAPK (36) (Fig 1)Studies have shown that the JNK and p38 MAPK pathways are mainlyrelated to stress and apoptosis of cells while the ERK/MAPKsignalling pathway which is the most thoroughly studied MAPKsignalling pathway is closely related to cell proliferation anddifferentiation and plays a pivotal role in the cell signaltransduction network (1128–30) Among all the signalling networks the MAPK signaltransmission pathway plays an important role in controlling variousphysiological processes in cells such as cell growth developmentdivision and death ERK is a member of the MAPK family and theERK/MAPK signalling pathway is the core of the signalling networkinvolved in regulating cell growth development and division Thebasic signal transmission steps follow the MAPK tertiary enzymaticcascade consisting of an upstream activator sequence MAP3K MAP2Kand MAPK In the ERK pathway Ras acts as an upstream activatingprotein Raf acts as MAP3K MAPK/ERK kinase (MEK) acts as MAPKK andERK is the MAPK forming the RasRafMEKERK pathway (31) ERK a type of serine/threonine protein kinase is asignal transduction protein that transmits mitogen signals(32) ERK is generally located inthe cytoplasm upon activation ERK enters the nucleus andregulates transcription factor activity and gene expression(33) Through artificial cloningand s Various stimulating factors such as cytokinesviruses Gproteincoupled receptor ligands and oncogenes playregulatory roles by activating the ERK/MAPK signalling pathway TheERK/MAPK signalling pathway can be activated through the followingways i) Ca2+activation ii) receptor tyrosine kinaseRas activation iii) PKCmediated activation and iv) Gproteincoupled receptor activation (77) ERK1/2 is located in the cytoplasm of unstimulatedcells Once activated ERK1/2 is transferred to the nucleus andregulates the activity of various transcription factors throughphosphorylation eventually regulating cell metabolism and functionand influencing the specific biological effects of cells (Fig 3) Cytoskeletal components such asmicrotubuleassociated protein (MAP) 1 MAP2 and MAP4 arephosphorylated in the cytoplasm to participate in the regulation ofcell morphology and cytoskeletal redistribution In the nucleusthe phosphorylation of nuclear transcription factors such asprotooncogene cFos protooncogene cJun ETS domaincontainingprotein Elk1 protooncogene cMyc and cyclic AMPdependenttranscription factor ATF2 Cytoplasmic ERK1/2 can phosphorylate aseries of other protein kinases upstream of the ERK pathway suchas SOS Raf1 and MEK in a negative feedback regulatory manner(Fig 4) Activation of ERK/MAPKsignalling pathways activates other extracellular signallin This review summarized how the ERK/MAPK signallingpathway affects the occurrence and development of human tumoursFurther studies will reveal additional details regarding the roleof MAPK signalling pathways in tumour pathogenesis The cellularsignalling pathway is a complex network Activation of a signallingmolecule by its downstream signal has biological effects such aspromoting or inhibiting tumour cell growth and invasion howeverthe regulatory mechanism of synergism or antagonism amongintracellular signalling pathways remains unclear The role ofsignalling pathways in cellular processes requires further analysisto clarify the role of signalling pathways in tumorigenesis anddevelopment This may further provide new methods for treatingtumours This study was supported by The Natural ScienceFoundation of Zhejiang Province (grant no LY17H160060) theNational Natural Science Foundation of China (grant nos 31871402and 81402162) the Experimental Animal Science and Technology PlanProjects of Zhejiang Province (grant no 2017C37173) and theCollege Student&#39s Science and Technology Innovation Project (grantno 2018R417024) YJG WWP and SBL conceived and designed the articleYX and ZFS analysed the relevant literature YJG wrote themanuscript and drew the figures YJG YX ZFS and LLH made revisedthe manuscript YJG WWP and SBL are responsible for textlayout Author Yan‑Jun Guo Wei‑Wei Pan Sheng‑Bing Liu Zhong‑Fei Shen Ying Xu Ling‑Ling HuCited by Publish Year 2020.

Extracellular SignalRegulated Kinases an overview

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Erk Signaling Pathway Creative Diagnostics

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ERK/MAPK Signaling Is Required for PathwaySpecific Striatal

ERK/MAPK deletion in D1RMSNs (direct pathway) resulted in decreased locomotor behavior reduced weight gain and early postnatal lethality In contrast loss of ERK/MAPK signaling in D2RMSNs (indirect pathway) resulted in a profound hyperlocomotor phenotype ERK/MAPKdeficient D2RMSNs exhibited a significant reduction in dendritic spine.