PMID- 10428811
OWN - NLM
STAT- MEDLINE
DCOM- 19990902
LR  - 20191210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 32
DP  - 1999 Aug 6
TI  - A tyrosine-phosphorylated protein that binds to an important regulatory region on
      the cool family of p21-activated kinase-binding proteins.
PG  - 22393-400
AB  - The p21-activated kinases (Pak) are major targets of the small GTPases Cdc42 and 
      Rac. We, and others, recently identified a family of proteins termed Cool/Pix,
      which interact with Pak3. In cells, p50(Cool-1) suppresses Pak activation by
      upstream activators; p85(Cool-1) has a permissive effect on Pak activation, and
      we now show that the closely related Cool-2 stimulates Pak kinase activity. To
      understand the differential regulation of Pak by Cool proteins, we screened for
      Cool-interacting proteins by affinity purification and microsequencing. This has 
      led to the identification of two closely related proteins called Cat
      (Cool-associated, tyrosine phosphorylated), which contain a zinc finger followed 
      by three ankyrin repeats. Cat-1 is identical to the recently identified binding
      partner for the beta-adrenergic receptor kinase (betaARK or GRK-2), which was
      shown to have Arf-GAP activity. Cat-1 and Cat-2 both bind to the COOH-terminal
      region of p85(Cool-1) and p85(Cool-2) but do not bind to p50(Cool-1). Cat-1 is
      tyrosine-phosphorylated in growing NIH 3T3 fibroblasts, and its tyrosine
      phosphorylation is increased following cell spreading on fibronectin, decreased
      in cells arrested in mitosis, and increased in the ensuing G(1) phase. Cat
      proteins are tyrosine-phosphorylated when co-expressed in cells with the focal
      adhesion kinase Fak and Src. These findings suggest that in addition to playing a
      role in Cool/Pak interactions, Cat proteins may serve as points of convergence
      between G protein-coupled receptors, integrins, Arf GTPases, cell cycle
      regulators, and Cdc42/Rac/Pak signaling pathways.
FAU - Bagrodia, S
AU  - Bagrodia S
AD  - Department of Molecular Medicine, Molecular and Cell Biology, Cornell University,
      Ithaca, New York 14853-6401, USA.
FAU - Bailey, D
AU  - Bailey D
FAU - Lenard, Z
AU  - Lenard Z
FAU - Hart, M
AU  - Hart M
FAU - Guan, J L
AU  - Guan JL
FAU - Premont, R T
AU  - Premont RT
FAU - Taylor, S J
AU  - Taylor SJ
FAU - Cerione, R A
AU  - Cerione RA
LA  - eng
SI  - GENBANK/AF148693
GR  - GM40654/GM/NIGMS NIH HHS/United States
GR  - GM47458/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 (ARHGEF6 protein, human)
RN  - 0 (ARHGEF7 protein, human)
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (GIT1 protein, human)
RN  - 0 (GTPase-Activating Proteins)
RN  - 0 (Git1 protein, mouse)
RN  - 0 (Git2 protein, mouse)
RN  - 0 (Guanine Nucleotide Exchange Factors)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Rho Guanine Nucleotide Exchange Factors)
RN  - EC 2.7.- (Protein Kinases)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding Sites
MH  - Cell Adhesion/*physiology
MH  - Cell Cycle/*physiology
MH  - Cell Cycle Proteins/*metabolism
MH  - Cloning, Molecular
MH  - Enzyme Activation
MH  - GTPase-Activating Proteins
MH  - *Guanine Nucleotide Exchange Factors
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins
MH  - Mice
MH  - Molecular Sequence Data
MH  - *Multigene Family
MH  - Phosphoproteins/*metabolism
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein Kinases/isolation & purification/*metabolism
MH  - Rho Guanine Nucleotide Exchange Factors
MH  - Sequence Analysis, DNA
MH  - Signal Transduction
EDAT- 1999/07/31 00:00
MHDA- 1999/07/31 00:01
CRDT- 1999/07/31 00:00
PHST- 1999/07/31 00:00 [pubmed]
PHST- 1999/07/31 00:01 [medline]
PHST- 1999/07/31 00:00 [entrez]
AID - 10.1074/jbc.274.32.22393 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Aug 6;274(32):22393-400. doi: 10.1074/jbc.274.32.22393.