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.
Fukuyama
K
K
Departments of Dermatology, 1st Internal Medicine, Molecular Biology, and Urology, Yokohama City University School of Medicine, 3-9, Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Yoshida
M
M
Yamashita
A
A
Deyama
T
T
Baba
M
M
Suzuki
A
A
Mohri
H
H
Ikezawa
Z
Z
Nakajima
H
H
Hirai
S
S
Ohno
S
S
D064413:3-Phosphoinositide-Dependent Protein Kinases; D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D006982:Hypertonic Solutions; D047908:Intracellular Signaling Peptides and Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D016350:Leucine Zippers; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D013012:Sorbitol / Q000494:pharmacology
D002352:Carrier Proteins; D006982:Hypertonic Solutions; D047908:Intracellular Signaling Peptides and Proteins; C411875:MBIP protein, human; D013012:Sorbitol; D064413:3-Phosphoinositide-Dependent Protein Kinases; D017346:Protein Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; C090757:mitogen-activated protein kinase kinase kinase 12