PMID- 10391949
OWN - NLM
STAT- MEDLINE
DCOM- 19990805
LR  - 20211203
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 28
DP  - 1999 Jul 9
TI  - Gi proteins use a novel beta gamma- and Ras-independent pathway to activate 
      extracellular signal-regulated kinase and mobilize AP-1 transcription factors in 
      Jurkat T lymphocytes.
PG  - 19992-20001
AB  - Receptors coupled to pertussis toxin (PTX)-sensitive Gi proteins regulate T 
      lymphocyte cytokine secretion, proliferation, and chemotaxis, yet little is known 
      about the molecular mechanisms of Gi protein signaling in mammalian lymphocytes. 
      Using the Jurkat T lymphocyte cell line, we found that a stably expressed Gi 
      protein-coupled receptor (the delta-opioid receptor (DOR1)) stimulates MEK-1 and 
      extracellular signal-regulated kinases 1 and 2 (ERK1 and ERK2) and 
      transcriptional activity by an ERK target, Elk-1, via a mechanism requiring a 
      PTX-sensitive Gi protein. Levels of beta-adrenergic receptor kinase-1 C-terminal 
      fragment that inhibited signaling by Gi protein beta gamma subunits in these 
      cells had no effect on DOR1 stimulation of either MEK-1- or Elk-1-dependent 
      transcription, indicating that this pathway is independent of beta gamma. 
      Analysis of this betagamma-independent pathway indicates a role for a herbimycin 
      A-sensitive tyrosine kinase. Unlike beta gamma-mediated pathways, the beta 
      gamma-independent pathway was insensitive to RasN17, inhibitors of 
      phosphatidylinositol 3-kinase (PI 3-kinase), and constitutive PI 3-kinase 
      activity. The beta gamma-independent pathway regulates downstream events, since 
      blocking it abrogated both Elk-1-dependent transcription and mobilization of the 
      mitogenic transcription factor, AP-1, in response to DOR1 signaling. These 
      results characterize a novel, Ras- and PI 3kinase-independent pathway for ERK 
      activation by Gi protein signaling that is distinct from ERK activation by beta 
      gamma and may therefore be mediated by the alphai subunit.
FAU - Hedin, K E
AU  - Hedin KE
AD  - Department of Immunology, The Mayo Clinic and Foundation, Rochester, Minnesota 
      55905, USA. hedin@mayo.edu
FAU - Bell, M P
AU  - Bell MP
FAU - Huntoon, C J
AU  - Huntoon CJ
FAU - Karnitz, L M
AU  - Karnitz LM
FAU - McKean, D J
AU  - McKean DJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Benzoquinones)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (ELK1 protein, human)
RN  - 0 (Lactams, Macrocyclic)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 0 (Quinones)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Opioid, delta)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Transcription Factors)
RN  - 0 (Virulence Factors, Bordetella)
RN  - 0 (ets-Domain Protein Elk-1)
RN  - 1W306TDA6S (Rifabutin)
RN  - 70563-58-5 (herbimycin)
RN  - EC 2.4.2.31 (Pertussis Toxin)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 2.7.11.15 (beta-Adrenergic Receptor Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 1)
RN  - EC 2.7.12.2 (MAP2K1 protein, human)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Benzoquinones
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/metabolism
MH  - *DNA-Binding Proteins
MH  - Enzyme Activation
MH  - GTP-Binding Proteins/*metabolism
MH  - Gene Expression Regulation
MH  - Humans
MH  - Jurkat Cells
MH  - Lactams, Macrocyclic
MH  - MAP Kinase Kinase 1
MH  - *Mitogen-Activated Protein Kinase Kinases
MH  - Pertussis Toxin
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Protein-Tyrosine Kinases/metabolism
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-fos/metabolism
MH  - Quinones/pharmacology
MH  - RNA, Messenger/metabolism
MH  - Receptors, Opioid, delta/metabolism
MH  - Rifabutin/analogs & derivatives
MH  - Signal Transduction
MH  - Transcription Factor AP-1/*metabolism
MH  - *Transcription Factors
MH  - Virulence Factors, Bordetella/pharmacology
MH  - beta-Adrenergic Receptor Kinases
MH  - ets-Domain Protein Elk-1
MH  - ras Proteins/*metabolism
EDAT- 1999/07/03 00:00
MHDA- 1999/07/03 00:01
CRDT- 1999/07/03 00:00
PHST- 1999/07/03 00:00 [pubmed]
PHST- 1999/07/03 00:01 [medline]
PHST- 1999/07/03 00:00 [entrez]
AID - S0021-9258(19)87124-7 [pii]
AID - 10.1074/jbc.274.28.19992 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Jul 9;274(28):19992-20001. doi: 10.1074/jbc.274.28.19992.