PMID- 10652228
OWN - NLM
STAT- MEDLINE
DCOM- 20000301
LR  - 20131121
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 268
IP  - 1
DP  - 2000 Feb 5
TI  - Activation of the guanine nucleotide exchange factor Dbl following ACK1-dependent
      tyrosine phosphorylation.
PG  - 141-7
AB  - Signals triggered by diverse receptors modulate the activity of Rho family
      proteins, although the regulatory mechanism remains largely unknown. On the basis
      of their biochemical activity as guanine nucleotide exchange factors (GEFs), Dbl 
      family proteins are believed to be implicated in the regulation of Rho family
      GTP-binding proteins in response to a variety of extracellular stimuli. Here we
      show that GEF activity of full-length proto-Dbl is enhanced upon tyrosine
      phosphorylation. When transiently coexpressed with the activated form of the
      non-receptor tyrosine kinase ACK1, a downstream target of Cdc42, Dbl became
      tyrosine-phosphorylated. In vitro GEF activity of Dbl toward Rho and Cdc42 was
      augmented following tyrosine phosphorylation. Moreover, accumulation of the
      GTP-bound form of Rho and Rac within the cell paralleled ACK-1-dependent tyrosine
      phosphorylation of Dbl. Consistently, activation of c-Jun N-terminal kinase
      downstream of Rho family GTP-binding proteins was also enhanced when Dbl was
      tyrosine-phosphorylated. Collectively, these findings suggest that the tyrosine
      kinase ACK1 may act as a regulator of Dbl, which in turn activates Rho family
      proteins.
CI  - Copyright 2000 Academic Press.
FAU - Kato, J
AU  - Kato J
AD  - Faculty of Bioscience, Tokyo Institute of Technology, Tokyohama, 226-8501, Japan.
FAU - Kaziro, Y
AU  - Kaziro Y
FAU - Satoh, T
AU  - Satoh T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Guanine Nucleotide Exchange Factors)
RN  - 0 (MCF2 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (TNK2 protein, human)
RN  - EC 3.6.5.2 (cdc42 GTP-Binding Protein)
RN  - EC 3.6.5.2 (rhoA GTP-Binding Protein)
SB  - IM
MH  - Animals
MH  - COS Cells
MH  - Cell Line
MH  - Enzyme Activation
MH  - Guanine Nucleotide Exchange Factors/chemistry/genetics/*metabolism
MH  - Humans
MH  - Phosphorylation
MH  - Protein-Tyrosine Kinases/genetics/*metabolism
MH  - Proto-Oncogene Proteins/chemistry/genetics/*metabolism
MH  - Recombinant Proteins/chemistry/genetics/metabolism
MH  - Signal Transduction
MH  - Transfection
MH  - Tyrosine/metabolism
MH  - cdc42 GTP-Binding Protein/genetics/metabolism
MH  - rhoA GTP-Binding Protein/genetics/metabolism
EDAT- 2000/02/01 09:00
MHDA- 2000/03/04 09:00
CRDT- 2000/02/01 09:00
PHST- 2000/02/01 09:00 [pubmed]
PHST- 2000/03/04 09:00 [medline]
PHST- 2000/02/01 09:00 [entrez]
AID - 10.1006/bbrc.2000.2106 [doi]
AID - S0006-291X(00)92106-5 [pii]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2000 Feb 5;268(1):141-7. doi: 10.1006/bbrc.2000.2106.