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.
Skip Nav Destination
Article navigation
13 December 1999
Report|
December 13 1999
A Novel Regulatory Mechanism of Map Kinases Activation and Nuclear Translocation Mediated by Pka and the Ptp-Sl Tyrosine Phosphatase
Carmen Blanco-Aparicio,
Carmen Blanco-Aparicio
aInstituto de Investigaciones Citológicas, 46010 Valencia, Spain
Search for other works by this author on:
Josema Torres,
Josema Torres
aInstituto de Investigaciones Citológicas, 46010 Valencia, Spain
Search for other works by this author on:
Rafael Pulido
Rafael Pulido
aInstituto de Investigaciones Citológicas, 46010 Valencia, Spain
Search for other works by this author on:
Carmen Blanco-Aparicio
aInstituto de Investigaciones Citológicas, 46010 Valencia, Spain
Josema Torres
aInstituto de Investigaciones Citológicas, 46010 Valencia, Spain
Rafael Pulido
aInstituto de Investigaciones Citológicas, 46010 Valencia, Spain
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.
Received:
September 15 1999
Revision Requested:
October 28 1999
Accepted:
October 29 1999
Online ISSN: 1540-8140
Print ISSN: 0021-9525
© 1999 The Rockefeller University Press
1999
The Rockefeller University Press
J Cell Biol (1999) 147 (6): 1129–1136.
Article history
Received:
September 15 1999
Revision Requested:
October 28 1999
Accepted:
October 29 1999
Connected Content
Citation
Carmen Blanco-Aparicio, Josema Torres, Rafael Pulido; A Novel Regulatory Mechanism of Map Kinases Activation and Nuclear Translocation Mediated by Pka and the Ptp-Sl Tyrosine Phosphatase. J Cell Biol 13 December 1999; 147 (6): 1129–1136. doi: https://doi.org/10.1083/jcb.147.6.1129
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionSuggested Content
See also
Email alerts
Advertisement
Advertisement