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

Citation
C. Blanco-aparicio et al., A novel regulatory mechanism of MAP kinases activation and nuclear translocation mediated by PKA and the PTP-SL tyrosine phosphatase, J CELL BIOL, 147(6), 1999, pp. 1129-1135
Citations number
36
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
JOURNAL OF CELL BIOLOGY
ISSN journal
0021-9525 → ACNP
Volume
147
Issue
6
Year of publication
1999
Pages
1129 - 1135
Database
ISI
SICI code
0021-9525(199912)147:6<1129:ANRMOM>2.0.ZU;2-M
Abstract
Protein tyrosine phosphatase PTP-SL retains mitogen-activated protein (MAP) kinases in the cytoplasm in an inactive form by association through a kina se interaction motif (KIM) and tyrosine dephosphorylation. The related tyro sine phosphatases PTP-SL and STEP were phosphorylated by the cAMP-dependent protein kinase A (PKA),The PKA phosphorylation site on PTP-SL was identifi ed 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 p38 alpha were impaired . Furthermore, treatment of COS-7 cells with PKA activators, or overexpress ion of the Ca catalytic subunit of PKA, inhibited the cytoplasmic retention of ERK2 and p38 alpha by wild-type PTP-SL, but not by a PTP-SL S231A mutan t. These findings support the existence of a novel mechanism by which PKA m ay regulate the activation and translocation to the nucleus of MAP kinases.