Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51812 (mitogen-activated protein)
 10,636 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A novel dual specificity phosphatase (DSP) designated LMW-DSP2 was cloned with a combination of reverse transcription-polymerase chain reaction and cDNA library screening strategies. The LMW-DSP2 open reading frame of 194 amino acids contained a single DSP catalytic domain but lacked the cdc25 homology domain, which is conserved in most known DSPs. Northern blot and reverse transcription-polymerase chain reaction analyses revealed that LMW-DSP2 was specifically expressed in testis. Recombinant LMW-DSP2 protein exhibited phosphatase activity toward an artificial low molecular weight substrate para-nitrophenyl phosphate, and the activity was inhibited completely by sodium orthovanadate but not sodium fluoride, pyrophosphate, and okadaic acid. The substitution of critical amino acid residues, aspartic acid and cysteine, resulted in a dramatic reduction of phosphatase activity. Transient transfection of LMW-DSP2 in COS7 cells resulted in the expression of a 21-kDa protein, and the phosphatase was shown to be distributed in both the cytosol and the nucleus. LMW-DSP2 dephosphorylated and deactivated p38, to a higher extent, and stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase 1/2 mitogen-activated protein kinases, in transfected COS7 cells and in vitro. Interestingly, mutation in a conserved docking motif of p38 and SAPK/JNK as well as in a cluster of aspartic acids of LMW-DSP2 did not affect the deactivation of the mitogen-activated protein kinases by LMW-DSP2. Furthermore, the binding between LMW-DSP2 and p38 and SAPK/JNK was also not disrupted by such mutations. Among the DSPs lacking the cdc25 homology domain, LMW-DSP2 is the first one that dephosphorylates and deactivates p38 and SAPK/JNK.
 ...
PMID:Molecular cloning and characterization of a novel dual specificity phosphatase, LMW-DSP2, that lacks the cdc25 homology domain. 2399 90

The smallest active protein-tyrosine phosphatase yet (only 16 kDa) is described here and given the name VHZ for VH1-like member Z because it belongs to the group of small Vaccinia virus VH1-related dual specific phosphatases exemplified by VHR, VHX, and VHY. Human VHZ is remarkably well conserved through evolution as it has species orthologs in frogs, fish, fly, and Archaea. The gene for VHZ, which we designate as DUSP25, is located on human chromosome 1q23.1 and consists of only two coding exons. VHZ is broadly expressed in tissues and cells, including resting blood lymphocytes, Jurkat T cells, HL-60, and RAMOS. In transfected cells, VHZ was located in the cytosol and in other cells also in the nucleoli. Endogenous VHZ showed a similar but more granular distribution. We show that VHZ is an active phosphatase and analyze its structure by computer modeling, which shows that in comparison with the 185-amino acid residue VHR, the 150-residue VHZ is a shortened version of VHR and contains the minimal set of secondary structure elements conserved in all known phosphatases from this class. The surface charge distribution of VHZ differs from that of VHR and is therefore unlikely to dephosphorylate mitogen-activated protein kinases. The remarkably high degree of conservation of VHZ through evolution may indicate a role in some ancient and fundamental physiological process.
 ...
PMID:The minimal essential core of a cysteine-based protein-tyrosine phosphatase revealed by a novel 16-kDa VH1-like phosphatase, VHZ. 1520 Dec 83