Mixed lineage kinase-3 (MLK-3) is a mitogen-activated kinase kinase kinase thatmediates stress-activating protein kinase (SAPK)/c-Jun NH2-terminal kinase activation.MLK-3 and other MLK family kinases are characterized by the presence of multipleprotein-protein interaction domains including a tandem leucine/isoleucine zipper (LZs)motif. Leucine zippers are known to mediate protein dimerization raising the possibilitythat the tandem leucine/isoleucine zippers may function as a dimerization motif ofMLK-3 (1). MLK-3 has several interesting structural features including an SH3 domain inthe absence of an SH2 domain, a region containing two leucine zippers with an adjacentcarboxy-terminal basic region, and a proline rich region. (2). HPK1 has been found tophosphorylate MLK-3 activation loop in vitro, and Ser281 was found to be the majorphosphorylation site, indicating that HPK1 also activates MLK-3 via phosphorylation ofthe kinase activation loop (3). Gene Symbol: MAP3K11
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