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MKK4, also known as JNKK1 and SEK1, is a dual specificity kinase that belongs to the Ser/Thr protein kinase family. MKK4 is a direct activator of MAP kinases in response to various environmental stresses or mitogenic stimuli. MKK4 phosphorylates and activates p38 MAP kinase and JNK but not ERK 1/2 (1-2). JNK is activated by dual phosphorylation at Thr and Tyr by MKK4 and MKK7; although MKK4 will preferentially phosphorylate Tyr (3). MKK4 is also known to be a tumor suppressor, as mutations inactivating the MKK4 gene have been found in 5% of a wide variety of tumor types (4).
