PMID- 10391903
OWN - NLM
STAT- MEDLINE
DCOM- 19990805
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 28
DP  - 1999 Jul 9
TI  - Gab2, a new pleckstrin homology domain-containing adapter protein, acts to
      uncouple signaling from ERK kinase to Elk-1.
PG  - 19649-54
AB  - We describe a novel human adapter molecule containing a pleckstrin homolgy (PH)
      domain at the N terminus that is closely related to human Grb2-associated binder 
      1, Gab1, and Drosophila daughter of sevenless. We designate this protein as Gab2.
      Northern blot analysis indicates that Gab2 is widely expressed and has an
      overlapping but distinctive expression pattern as compared with Gab1, with high
      levels of Gab2 mRNA detected in the heart, brain, placenta, spleen, ovary,
      peripheral blood leukocytes, and spinal cord. Upon tyrosine phosphorylation, Gab2
      physically interacts with Shp2 tyrosine phosphatase and Grb2 adapter protein.
      Strikingly, Gab2 has an inhibitory effect on the activation of Elk-1-dependent
      transcription triggered by a dominant active Ras mutant (RasV12) or under growth 
      factor stimulation, whereas Gab1 acts to potentiate slightly the Elk-1 activity
      in the same system. In contrast to the reciprocal effects of Gab1 and Gab2 in
      mediating Elk-1 induction, these two molecules have a similar function in
      extracellular signal-regulated kinase activation induced by either oncogenic Ras 
      or growth factor stimulation. Taken together, these results argue that Gab1 and
      Gab2, two closely related PH-containing adapter proteins, might have distinct
      roles in coupling cytoplasmic-nuclear signal transduction. This is the first
      evidence that an intracellular molecule with a PH domain operates as a negative
      effector in signal relay to the regulation of gene expression.
FAU - Zhao, C
AU  - Zhao C
AD  - Department of Biochemistry and Molecular Biology, and Walther Oncology Center,
      Indiana University School of Medicine, Indianapolis, Indiana 46202-5254, USA.
FAU - Yu, D H
AU  - Yu DH
FAU - Shen, R
AU  - Shen R
FAU - Feng, G S
AU  - Feng GS
LA  - eng
GR  - R29GM53660/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (ELK1 protein, human)
RN  - 0 (GAB2 protein, human)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Potassium Channels)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - 0 (ets-Domain Protein Elk-1)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 3.1.3.48 (PTPN11 protein, human)
RN  - EC 3.1.3.48 (PTPN6 protein, human)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 6)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Cell Line
MH  - Cloning, Molecular
MH  - *DNA-Binding Proteins
MH  - Enzyme Activation
MH  - Gene Expression Regulation
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - Molecular Sequence Data
MH  - Phosphoproteins/chemistry/*genetics/metabolism
MH  - Phosphorylation
MH  - Potassium Channels/*metabolism
MH  - Protein Binding
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 11
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 6
MH  - Protein Tyrosine Phosphatases/metabolism
MH  - *Proto-Oncogene Proteins
MH  - RNA, Messenger/metabolism
MH  - Sequence Alignment
MH  - Signal Transduction
MH  - *Transcription Factors
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 - 10.1074/jbc.274.28.19649 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Jul 9;274(28):19649-54. doi: 10.1074/jbc.274.28.19649.