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The MEKK3–MEK5–ERK5–KLF2/4 signalling pathway. Loss of KRIT1 or CCM2, activation of cdc42 or TLR4, or other stimuli can result in hyperactivation of the MEKK3–MEK5–ERK5 kinase cascade, leading to upregulation of KLF2 and KLF4 transcription factors and changes in expression of their transcriptional targets such as ADAMTS4, thrombomodulin (TM), thrombospondin 1 (TSP1), bone morphogenic protein 6 (BMP6) and potentially SLC39.
