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J. Cell Biol. 147 (6): 1129-1136

Copyright © 1999 by the Rockefeller University Press.

Brief Report

A Novel Regulatory Mechanism of Map Kinases Activation and Nuclear Translocation Mediated by Pka and the Ptp-Sl Tyrosine Phosphatase

Carmen Blanco-Aparicioa, Josema Torresa, , and Rafael Pulidoa

a Instituto de Investigaciones Citológicas, 46010 Valencia, Spain
Instituto de Investigaciones Citológicas, Amadeo de Saboya, 4, 46010 Valencia, Spain.34-96-360145334-96-3391256

rpulido{at}ochoa.fib.es

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 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 p38{alpha} were impaired. Furthermore, treatment of COS-7 cells with PKA activators, or overexpression of the C{alpha} 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 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.

Key Words: MAP kinases • PKA • PTP-SL • tyrosine phosphatases • signal transduction

C. Blanco-Aparicio and J. Torres contributed equally to this work.

Abbreviations used in this paper: cPKA, PKA catalytic subunit; ERK, extracellular signal–regulated kinase; GST, glutathione-S-transferase; HA, hemagglutinin; JNK, c-Jun NH2-terminal kinase; KIM, kinase interaction motif; MAP, mitogen-activated protein; PKA, protein kinase A; PKC, protein kinase C; PTP, protein tyrosine phosphatase.

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