Abstract
Protein tyrosine phosphatase PTP-SL retains mitogen-activated protein (MAP) kinases in the cytoplasm in an inactive form by association through a kinase interaction motif (KIM) and tyrosine dephosphorylation. The related tyrosine phosphatases PTP-SL and STEP were phosphorylated by the cAMP-dependent protein kinase A (PKA). The PKA phosphorylation site on PTP-SL was identified as the Ser(231) residue, located within the KIM. Upon phosphorylation of Ser(231), PTP-SL binding and tyrosine dephosphorylation of the MAP kinases extracellular signal-regulated kinase (ERK)1/2 and p38alpha were impaired. Furthermore, treatment of COS-7 cells with PKA activators, or overexpression of the Calpha catalytic subunit of PKA, inhibited the cytoplasmic retention of ERK2 and p38alpha by wild-type PTP-SL, but not by a PTP-SL S231A mutant. These findings support the existence of a novel mechanism by which PKA may regulate the activation and translocation to the nucleus of MAP kinases.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Motifs
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Animals
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Biological Transport
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COS Cells
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Cell Line
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Cell Nucleus / enzymology*
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Cell Nucleus / metabolism*
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Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
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Cyclic AMP-Dependent Protein Kinases / chemistry
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Cyclic AMP-Dependent Protein Kinases / genetics
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Cyclic AMP-Dependent Protein Kinases / metabolism*
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Cytoplasm / enzymology
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Cytoplasm / metabolism
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Enzyme Activation
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Humans
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Intracellular Signaling Peptides and Proteins
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Mitogen-Activated Protein Kinase 1 / genetics
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases / genetics
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Mitogen-Activated Protein Kinases / metabolism*
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Models, Biological
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Mutation / genetics
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Phosphorylation
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Phosphoserine / metabolism
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Protein Tyrosine Phosphatases / chemistry
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Protein Tyrosine Phosphatases / genetics
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Protein Tyrosine Phosphatases / metabolism*
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Protein Tyrosine Phosphatases, Non-Receptor
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Receptor-Like Protein Tyrosine Phosphatases, Class 7
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / metabolism
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Signal Transduction
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Transfection
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p38 Mitogen-Activated Protein Kinases
Substances
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Intracellular Signaling Peptides and Proteins
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Nerve Tissue Proteins
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Recombinant Fusion Proteins
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Phosphoserine
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Cyclic AMP-Dependent Protein Kinases
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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PTPN5 protein, human
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PTPRR protein, human
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Protein Tyrosine Phosphatases
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Protein Tyrosine Phosphatases, Non-Receptor
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Receptor-Like Protein Tyrosine Phosphatases, Class 7