PMID- 10559944
OWN - NLM
STAT- MEDLINE
DCOM- 19991206
LR  - 20131121
IS  - 1465-7392 (Print)
IS  - 1465-7392 (Linking)
VI  - 1
IP  - 5
DP  - 1999 Sep
TI  - Crosstalk between cAMP-dependent kinase and MAP kinase through a protein tyrosine
      phosphatase.
PG  - 305-11
AB  - The haematopoietic protein tyrosine phosphatase (HePTP) is a negative regulator
      of the MAP kinases Erk1, Erk2 and p38. HePTP binds to these kinases through a
      kinase-interaction motif (KIM) in its non-catalytic amino terminus and
      inactivates them by dephosphorylating the critical phosphorylated tyrosine
      residue in their activation loop. Here we show that cyclic-AMP-dependent protein 
      kinase (PKA) phosphorylates serine residue 23 in the KIM of HePTP in vitro and in
      intact cells. This modification reduces binding of MAP kinases to the KIM, an
      effect that is prevented by mutation of serine 23 to alanine. The PKA-mediated
      release of MAP kinase from HePTP is sufficient to activate the kinase and to
      induce transcription from the c-fos promoter. Expression of a HePTP
      serine-23-to-alanine mutant inhibits MAP-kinase dissociation and activation and
      induction of transcription from the c-fos promoter. We conclude that HePTP not
      only controls the activity of MAP kinases, but also mediates crosstalk between
      the cAMP system and the MAP-kinase cascade.
FAU - Saxena, M
AU  - Saxena M
AD  - Laboratory of Signal Transduction, Sidney Kimmel Cancer Center, San Diego,
      California 92121, USA.
FAU - Williams, S
AU  - Williams S
FAU - Tasken, K
AU  - Tasken K
FAU - Mustelin, T
AU  - Mustelin T
LA  - eng
GR  - AI35603/AI/NIAID NIH HHS/United States
GR  - AI40552/AI/NIAID NIH HHS/United States
GR  - AI41481/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nat Cell Biol
JT  - Nature cell biology
JID - 100890575
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.1.3.48 (PTPN6 protein, human)
RN  - EC 3.1.3.48 (PTPN7 protein, human)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 6)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases, Non-Receptor)
RN  - OF5P57N2ZX (Alanine)
SB  - IM
MH  - Alanine
MH  - Amino Acid Substitution
MH  - Cyclic AMP-Dependent Protein Kinases/chemistry/*metabolism
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - Jurkat Cells
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3
MH  - Mitogen-Activated Protein Kinases/chemistry/*metabolism
MH  - Models, Chemical
MH  - Mutagenesis, Site-Directed
MH  - Phosphorylation
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 6
MH  - Protein Tyrosine Phosphatases/*metabolism
MH  - Protein Tyrosine Phosphatases, Non-Receptor
MH  - Recombinant Proteins/chemistry/metabolism
MH  - Serine
MH  - Signal Transduction
MH  - Substrate Specificity
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 1999/11/13 09:00
MHDA- 2001/03/23 10:01
CRDT- 1999/11/13 09:00
PHST- 1999/11/13 09:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/11/13 09:00 [entrez]
AID - 10.1038/13024 [doi]
PST - ppublish
SO  - Nat Cell Biol. 1999 Sep;1(5):305-11. doi: 10.1038/13024.