mitogen-activated protein kinase kinase kinase 11 (mixed lineage kinase 3, src-homology 3 domain-containing proline-rich kinase, MAP3K11, MLK3, SPRK)
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Function
- activates the JUN N-terminal pathway
- required for serum-stimulated cell proliferation & for mitogen & cytokine activation of MAPK14 (p38), MAPK3 (ERK) & MAPK8 (JNK1)
- plays a role in mitogen-stimulated phosphorylation & activation of BRAF, but does not phosphorylate BRAF directly
- influences microtubule organization during the cell cycle
- homodimerization via the leucine zipper domains is required for autophosphorylation & subsequent activation
- autophosphorylation on Ser & Thr within the activation loop plays a role in enzyme activation
- Thr-277 is likely to be the main autophosphorylation site
- phosphorylation of Ser-555 & Ser-556 is induced by CDC42
ATP + a protein <--> ADP + a phosphoprotein
Cofactor: Mg+2 (putative)
Structure
- homodimer
- undergoes dimerization during activation
- belongs to the protein kinase superfamily, STE Ser/Thr protein kinase family, MAP kinase kinase kinase subfamily
- contains 1 protein kinase domain contains 1 SH3 domain
Compartment
- centrosome
- location is cell cycle dependent
Expression
- expressed in a wide variety of normal & neoplastic tissues including fetal lung, liver, heart & kidney, & adult lung, liver, heart, kidney, placenta, skeletal muscle, pancreas & brain