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The Ras signaling pathway links the signals from growth factor receptors with the activation of the MAPK kinase cascade of phosphorylation leading to cell growth and differentiation. External stimuli, like endotoxins, UV irradiation, heat, and hyperosmolarity, induce an array of cellular responses that culminate with gene expression, ultimately dictating an adaptation to the new environment. Small GTPases of the Rho family, including cdc42, Rac1, and Rho, transmit the stress signals that initiate the signal cascade. JNK is a c-Jun kinase that was also identified as SAPK1 and MAPKp49. JNK/SAPK, along with p38 and RK5/BMK1, comprise three classes of stress-activated MAPK groups. Complete activation of JNK/SAPK requires the phosphorylation of both Thr183 and Tyr185, which are located in a Thr-X-Tyr motif. The activation of these residues is believed to be carried out by MKK4 and MKK7. Active JNK/SAPK phosphorylates other kinases and multiple transcription factors that induce expression of genes, such as proinflammatory cytokines.Flow Cytometry, Western Blotting
