Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
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Gene/Protein
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Target Concepts:
Gene/Protein
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Query: EC:2.5.1.18 (
glutathione S-transferase
)
22,582
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
A novel cDNA encoding PTP (protein tyrosine phosphatase) was cloned from PC12h cells and designated as
PCPTP1
(gene encoding PC12 protein Tyr phosphatase). The longest open reading frame (ORF) of this clone encodes a 656-amino-acid (aa) protein with a single PTP catalytic domain. Western blot analysis using a polyclonal Ab (antibody) raised against the cytoplasmic region of
PCPTP1
detected two products, a major 65-kDa and minor 42-kDa protein, designated
PCPTP1
-MFI and
PCPTP1
-MVQ, respectively, in PC12h cells. These two proteins correspond to the products translated from the second and fifth methionine of
PCPTP1
, respectively. The bacterially expressed
GST
::
PCPTP1
-MVQ fusion protein had phosphatase activity with pNPP (p-nitrophenyl phosphate) as a substrate. Alignment of the aa sequence of
PCPTP1
-MVQ with those of other PTP showed the highest similarity to STEP and LC-PTP/HePTP, with 54 and 51% identity, respectively. Northern blot analysis showed only one 3.9-kb transcript in PC12h cells, indicating that
PCPTP1
corresponds to this 3.9-kb transcript. The 3.9-kb
PCPTP1
mRNA was detected in the brain and adrenal gland, but not in other non-neuronal tissues in adult rats. Two other transcripts of 3.3 and 1.7 kb were also detected in brain. NGF (nerve growth factor) and glucocorticoid are known to bimodally regulate the cell fate decision of sympathoadrenal precursors like PC12 cells, with NGF promoting the neuronal phenotype and glucocorticoid promoting the chromaffin phenotype. Still, both agents decreased the level of
PCPTP1
mRNA in PC12h cells. Therefore, it is likely that the decrease in the level of
PCPTP1
mRNA might be associated or correlated with cell differentiation in PC12h cells.
...
PMID:Cloning and expression of PCPTP1 encoding protein tyrosine phosphatase. 755 44
ERK1 and ERK2 associate with the tyrosine phosphatase
PTP-SL
through a kinase interaction motif (KIM) located in the juxtamembrane region of
PTP-SL
. A
glutathione S-transferase
(
GST
)-
PTP-SL
fusion protein containing the KIM associated with ERK1 and ERK2 as well as with p38/HOG, but not with the related JNK1 kinase or with protein kinase A or C. Accordingly, ERK2 showed in vitro substrate specificity to phosphorylate
GST
-
PTP-SL
in comparison with
GST
-c-Jun. Furthermore, tyrosine dephosphorylation of ERK2 by the PTP-SLDeltaKIM mutant was impaired. The in vitro association of ERK1/2 with
GST
-
PTP-SL
was highly stable; however, low concentrations of nucleotides partially dissociated the ERK1/2.
PTP-SL
complex. Partial deletions of the KIM abrogated the association of
PTP-SL
with ERK1/2, indicating that KIM integrity is required for interaction. Amino acid substitution analysis revealed that Arg and Leu residues within the KIM are essential for the interaction and suggested a regulatory role for Ser(231). Finally, coexpression of
PTP-SL
and ERK2 in COS-7 cells resulted in the retention of ERK2 in the cytoplasm in a KIM-dependent manner. Our results demonstrate that the noncatalytic region of
PTP-SL
associates with mitogen-activated protein kinases with high affinity and specificity, providing a mechanism for substrate specificity, and suggest a role for
PTP-SL
in the regulation of mitogen-activated protein kinase translocation to the nucleus upon activation.
...
PMID:Interaction of mitogen-activated protein kinases with the kinase interaction motif of the tyrosine phosphatase PTP-SL provides substrate specificity and retains ERK2 in the cytoplasm. 1041 10
