the flutter shifts spontaneously to fibrillation as time progresses

The Ras GTP complex has the capacity to initialize the RAF kinase, a MAP kinase kinase kinase that is an upstream compo nent of the ERK pathway, which phosphorylates the MEK kinase and, subsequently, phosphorylates and activates another pathway component MAPKERK, The RTKs that connect to Ras, or other members of its superfamily, are varied and range from the epidermal growth factor receptor, Dasatinib BMS-354825 c Set, platelet-derived growth fac tor receptor, vascular endothelial growth factor receptor, fibroblast growth factor receptor, and fms related tyrosine kinase 3, JNKs can be initialized by the upstream MKK4 and MKK7 kinases, Though there are several JNK substrates, it is still chal lenging to recognize the molecular networks regulated by the patient JNK family members. It has been found that JNK signaling can alternatively result in apoptosis or cell survival, Downstream targets of the MAPKs contain p53, c Fos, and c Jun, c Jun and c Fos Meristem form a complex named AP 1 that works like a transcription factor. MAPKs can translocate towards the nucleus and then phos phorylate AP 1 transcription factors to mediate expression of target genes containing a TPA DNA response element, six. 2. Walkway Interruptions Associated with PCa and Therapeutic Targets. MAPKERK pathway is been shown to be activated in PCa, particularly in later TCID stages of the disease, and is often deregulated with AKT signaling, The upstream events that lead to activation of MAPK signaling aren't well defined but are perhaps related to aberrant growth factor signaling, While members of the Ras family are rarely mutated in PCa, Ras and the MEKERK pathway are triggered by EGF, IGF 1, KGF, and FGFs, which are often overexpressed in PCa, The expression of Ras or its effector loop mutants lessens the androgen dependent requirement of LNCaP cells for growth and improves their PSA expression and tumorigenicity, whereas dominant neg ative N17 Ras could reestablish androgen sensitivity to the CRPCa C4 2 cell line, Significantly, expression of activated forms of Ras or Raf in the mouse prostate epithelium results in PCa configuration, Curiously, a small percentage of aggressive PCa includes chromosome translocations involv 's w or c Raf, which results in a constitutively activated cross protein as a result of loss of the N terminal RAS binding domain, which implies that perturbations of Ras or Raf signaling may occur in PCa through systems apart from initiating mutations.