The MAP-Kinase (MAPK) signalling pathway

the map kinase signaling pathway the map kinase signaling pathway in the normal cell the designation map kinase abbreviated map K originates from one of the first members of this protein family the mitogen-activated protein kinase the map kinase pathway begins with the binding of a ligand for example EGF to the extracellular portion of a membrane bound receptor of the family of receptor tyrosine kinase –is abbreviated rtks ligand binding leads to the dimerization of two subunits of the receptor tyrosine kinase at the inner side of the receptor tyrosine kinase domains catalyze phosphorylation of itself and also of the other subunit next the growth factor receptor bound protein to grab – for short can bind to the phosphorylated RTK the protein s OS named after its homologue son of seven lists in drosophila is able to bind to the membrane bound protein Raz inactive rasz is bound to the nucleotide guanosine diphosphate gdp SOS catalyzes the exchange of the raspberry DP against GTP guanosine triphosphate this exchange leads to the activation of the rasz protein in its active GTP bound State Raz is able to bind to several effector proteins the kinase b raf is one of the most important effectors of r as active b raf phosphorylates and activates the kinase is mek 1 & 2 which in turn phosphorylate and activate the kinase a–‘s work 1 & 2 finally the kinase cascade leads to the activation of transcription factors of the ap1 family the abbreviation ap1 stands for activator protein one the best-known ap1 proteins are the transcription factors June and false after their activation June and Foss moved to the cell nucleus where they form a heterodimer and bind to an AP one motif of the DNA this leads to the expression of many genes and coding for example growth factors cyclones and cytokines as a direct consequence cell proliferation is activated in the normal cell the active razzed GTP complex is inactivated shortly after its activation in this way a permanently active map kinase signaling pathway and undesirable effects are avoided rasz gtp is inactivated by the GTP A’s activating protein also known as gap gap binds to R as gtp and increases the very weak gtp A’s activity of R as by several orders of magnitude gap achieves this activation by providing a domain that assists the R as protein in the hydrolysis of gtp the bound GTP is hydrolyzed to GDP GDP bound R as is no longer active and can no longer bind to be RAF as a result the map k sigma lling pathway is turned off the map K signaling pathway in a tumor cell with razz mutation mutation of the R as seen may have dramatic consequences for the cell mutated R as protein is activated just like the normal protein mutated active R as gtp is also able to bind and to activate the kinase b-raf a major difference between the mutated and the normal R as gtp protein is that the mutated protein loses its capability to be inactivated by the gtp A’s activating protein gap gap can still bind to mutated R as in its gtp-bound form however gap is not able to provide the domain that is crucial for the activation of the razzed gtp a s gtp is not hydrolyzed to GDP consequently mutated R as gtp stays active the kinase b raf stays bound to R as gtp and remains active b raf phosphorylates and activates an increasing number of mek one and two proteins in turn mek one and two activate erk1 and 2 which activate jun and false thus the kinase cascade is not turned off a permanently activated map kinase signaling pathway results in continuously activated proliferation which is an important feature of a tumor cell

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