A novel regulatory mechanism of MAP kinases activation and nuclear translocation mediated by PKA and the PTP-SL tyrosine phosphatase

6533b82dfe1ef96bd1290a11

RESEARCH PRODUCT

A novel regulatory mechanism of MAP kinases activation and nuclear translocation mediated by PKA and the PTP-SL tyrosine phosphatase

Carmen Blanco-aparicio Josema Torres Rafael Pulido

subject

Cytoplasm animal structures Recombinant Fusion Proteins Cèl·lules Amino Acid Motifs Nerve Tissue Proteins Protein tyrosine phosphatase SH2 domain Transfection environment and public health Models Biological p38 Mitogen-Activated Protein Kinases Receptor tyrosine kinase SH3 domain Cell Line Phosphoserine tyrosine phosphatases Animals Humans Protein phosphorylation PKA Receptor-Like Protein Tyrosine Phosphatases Class 7 Phosphorylation PTP-SL Cell Nucleus Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 biology Brief Report Intracellular Signaling Peptides and Proteins Biological Transport Cell Biology Protein Tyrosine Phosphatases Non-Receptor Cyclic AMP-Dependent Protein Kinases Enzyme Activation enzymes and coenzymes (carbohydrates)MAP kinases Biochemistry Mitogen-activated protein kinase COS Cells Mutation biology.protein Phosphorylation Mitogen-Activated Protein Kinases Protein Tyrosine Phosphatases Enzims signal transduction Proto-oncogene tyrosine-protein kinase Src

description

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 Ser231 residue, located within the KIM. Upon phosphorylation of Ser231, PTP-SL binding and tyrosine dephosphorylation of the MAP kinases extracellular signal–regulated kinase (ERK)1/2 and p38α were impaired. Furthermore, treatment of COS-7 cells with PKA activators, or overexpression of the Cα catalytic subunit of PKA, inhibited the cytoplasmic retention of ERK2 and p38α 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.

year	journal	country	edition	language
1999-12-22

10.1083/jcb.147.6.1129 https://hdl.handle.net/10550/84390