PMID:10601328

Citation	Blanco-Aparicio, C, Torres, J and Pulido, R (1999) A novel regulatory mechanism of MAP kinases activation and nuclear translocation mediated by PKA and the PTP-SL tyrosine phosphatase. J. Cell Biol. 147:1129-36
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.
Links	PubMed PMC2168101
Keywords	Amino Acid Motifs; Animals; Biological Transport; COS Cells; Cell Line; Cell Nucleus/enzymology; Cell Nucleus/metabolism; Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors; Cyclic AMP-Dependent Protein Kinases/chemistry; Cyclic AMP-Dependent Protein Kinases/genetics; Cyclic AMP-Dependent Protein Kinases/metabolism; Cytoplasm/enzymology; Cytoplasm/metabolism; Enzyme Activation; Humans; Intracellular Signaling Peptides and Proteins; Mitogen-Activated Protein Kinase 1/genetics; Mitogen-Activated Protein Kinase 1/metabolism; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases/genetics; Mitogen-Activated Protein Kinases/metabolism; Models, Biological; Mutation/genetics; Nerve Tissue Proteins/chemistry; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Phosphorylation; Phosphoserine/metabolism; Protein Tyrosine Phosphatases/chemistry; Protein Tyrosine Phosphatases/genetics; Protein Tyrosine Phosphatases/metabolism; Protein Tyrosine Phosphatases, Non-Receptor; Receptor-Like Protein Tyrosine Phosphatases, Class 7; Recombinant Fusion Proteins/chemistry; Recombinant Fusion Proteins/metabolism; Signal Transduction; Transfection; p38 Mitogen-Activated Protein Kinases
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