MKP-8, a novel MAPK phosphatase that inhibits p38 kinase.
Intracellular signaling pathways and their relationship to malignant progression have become a major focus of cancer biology. The dual-specificity phosphatase (DSP) family is a more recently identified family of intracellular signaling modulators. We have identified a novel protein phosphatase with a well-conserved DSP catalytic domain containing the DSP catalytic motif, xHCxxGxSRS, and mitogen-activated protein kinase phosphatase (MKP) motif, AYLM. Because of these unique characteristics, the protein was named mitogen-activated protein kinase phosphatase-8 (MKP-8). This protein is approximately 20kDa in size and mainly localizes to the nuclear compartment of the cell. MKP-8 is expressed in embryonal cancers (retinoblastoma, neuroepithelioma, and neuroblastoma) and has limited expression in normal tissues. MKP-8 displays significant phosphatase activity that is inhibited by a cysteine to serine substitution in the catalytic domain. When co-expressed with activated MAPKs, MKP-8 is able to inhibit p38 kinase phosphorylation and downstream activity.
Vasudevan
Sanjeev A
SA
Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
Skoko
John
J
Wang
Kuan
K
Burlingame
Susan M
SM
Patel
Parul N
PN
Lazo
John S
JS
Nuchtern
Jed G
JG
Yang
Jianhua
J
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D020134:Catalytic Domain; D003001:Cloning, Molecular; D017931:DNA Primers; D054637:Dual-Specificity Phosphatases; D006801:Humans; D054639:Mitogen-Activated Protein Kinase Phosphatases; D008969:Molecular Sequence Data; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry
D017931:DNA Primers; D048051:p38 Mitogen-Activated Protein Kinases; D054639:Mitogen-Activated Protein Kinase Phosphatases; C500883:DUSP26 protein, human; D054637:Dual-Specificity Phosphatases; D017027:Protein Tyrosine Phosphatases