MAPK upstream kinase (MUK)-binding inhibitory protein, a negative regulator of MUK/dual leucine zipper-bearing kinase/leucine zipper protein kinase.

Mitogen-activated protein kinase upstream kinase/dual leucine zipper-bearing kinase/leucine-zipper protein kinase (MUK/DLK/ZPK) is a MAPKKK class protein kinase that induces JNK/SAPK activation. We report here a protein named MBIP that binds to MUK/DLK/ZPK. MUK-binding inhibitory protein (MBIP) contains two tandemly orientated leucine-zipper-like motifs with a cluster of basic amino acids located ...
between the two motifs. MBIP interacts with one of the two leucine-zipper-like motifs of MUK/DLK/ZPK and inhibits the activity of MUK/DLK/ZPK to induce JNK/SAPK activation. Notably, no similar effect was observed with another JNK/SAPK-inducing MAPKKK, COT/Tpl-2, showing the specificity of MBIP action. Furthermore, the overexpression of MBIP partially inhibits the activation of JNK by 0.3 m sorbitol in 293T cells. Taken together, these observations indicate that MBIP can function as a regulator of MUK/DLK/ZPK, a finding that may provide a clue to understanding the molecular mechanism of JNK/SAPK activation by hyperosmotic stress.
Mesh Terms:
Amino Acid Sequence, Base Sequence, Carrier Proteins, Cell Line, Enzyme Activation, Humans, Hypertonic Solutions, Intracellular Signaling Peptides and Proteins, JNK Mitogen-Activated Protein Kinases, Leucine Zippers, MAP Kinase Kinase Kinases, Mitogen-Activated Protein Kinases, Molecular Sequence Data, Protein Conformation, Protein-Serine-Threonine Kinases, Signal Transduction, Sorbitol
J. Biol. Chem.
Date: Jul. 14, 2000
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