PMID- 10194762
OWN - NLM
STAT- MEDLINE
DCOM- 19990527
LR  - 20131121
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 13
IP  - 4
DP  - 1999 Apr
TI  - Extracellular signal-regulated kinase (ERK) interacts with signal transducer and 
      activator of transcription (STAT) 5a.
PG  - 555-65
AB  - Serine phosphorylation of signal transducers and activators of transcription
      (STAT) 1 and 3 modulates their DNA-binding capacity and/or transcriptional
      activity. Earlier we suggested that STAT5a functional capacity could be
      influenced by the mitogen-activated protein kinase (MAPK) pathway. In the present
      study, we have analyzed the interactions between STAT5a and the MAPKs,
      extracellular signal-regulated kinases ERK1 and ERK2. GH treatment of Chinese
      hamster ovary cells stably transfected with the GH receptor (CHOA cells) led to
      rapid and transient activation of both STAT5a and ERK1 and ERK2. Pretreatment of 
      cells with colchicine, which inhibits tubulin polymerization, did not inhibit
      STAT5a translocation to the nucleus and ERK1/2 activation. In vitro precipitation
      with a glutathione-S-transferase-fusion protein containing the C-terminal
      transactivation domain of STAT5a showed GH-regulated association of ERK1/2 with
      the fusion protein, while this was not seen when serine 780 in STAT5a was changed
      to alanine. In vitro phosphorylation of the glutathione-S-transferase-fusion
      proteins using active ERK only worked when the fusion protein contained wild-type
      STAT5a sequence. The same experiment, performed with full-length wild-type STAT5a
      and the corresponding S780A mutant, showed that serine 780 is the only substrate 
      in full-length STAT5a for active ERK. In coimmunoprecipitation experiments,
      larger amounts of STAT5a-ERK1/2 complexes were detected in cytosol from untreated
      CHOA cells than in cytosol from GH-treated cells, suggesting the presence of
      preformed STAT5a-ERK1/2 complexes in unstimulated cells. Transfection experiments
      with COS cells showed that kinase-inactive ERK1 decreased GH stimulation of
      STAT5-regulated reporter gene expression. These observations show, for the first 
      time, direct physical interaction between ERK and STAT5a and also clearly
      identify serine 780 as a target for ERK. Furthermore, it is also established that
      serine phosphorylation of STAT5a transactivation domain, via the MAPK pathway, is
      a means of modifying GH-induced transcriptional activation.
FAU - Pircher, T J
AU  - Pircher TJ
AD  - Department of Medical Nutrition, Karolinska Institute, Novum, Huddinge, Sweden.
FAU - Petersen, H
AU  - Petersen H
FAU - Gustafsson, J A
AU  - Gustafsson JA
FAU - Haldosen, L A
AU  - Haldosen LA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Milk Proteins)
RN  - 0 (Peptide Fragments)
RN  - 0 (Recombinant Proteins)
RN  - 0 (STAT5 Transcription Factor)
RN  - 0 (Trans-Activators)
RN  - 12629-01-5 (Human Growth Hormone)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
SB  - IM
MH  - Animals
MH  - Biological Transport
MH  - CHO Cells/drug effects/metabolism
MH  - Calcium-Calmodulin-Dependent Protein Kinases/drug effects/isolation &
      purification/*metabolism
MH  - Cell Nucleus/metabolism
MH  - Chemical Precipitation
MH  - Cricetinae
MH  - DNA-Binding Proteins/genetics/isolation & purification/*metabolism
MH  - Enzyme Activation/drug effects
MH  - Human Growth Hormone/metabolism/pharmacology
MH  - Microtubules/metabolism
MH  - *Milk Proteins
MH  - Peptide Fragments/metabolism
MH  - Phosphorylation
MH  - Recombinant Proteins/genetics/metabolism
MH  - STAT5 Transcription Factor
MH  - Serine
MH  - Trans-Activators/genetics/isolation & purification/*metabolism
EDAT- 1999/04/09 00:00
MHDA- 1999/04/09 00:01
CRDT- 1999/04/09 00:00
PHST- 1999/04/09 00:00 [pubmed]
PHST- 1999/04/09 00:01 [medline]
PHST- 1999/04/09 00:00 [entrez]
AID - 10.1210/mend.13.4.0263 [doi]
PST - ppublish
SO  - Mol Endocrinol. 1999 Apr;13(4):555-65. doi: 10.1210/mend.13.4.0263.