PMID- 10523848
OWN - NLM
STAT- MEDLINE
DCOM- 19991122
LR  - 20211203
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 41
DP  - 1999 Oct 7
TI  - alphaPIX nucleotide exchange factor is activated by interaction with
      phosphatidylinositol 3-kinase.
PG  - 5680-90
AB  - p21-activated kinase (PAK) is a common effector protein of the small GTPases
      Cdc42 and Rac, leading to the activation of downstream mitogen activated protein 
      kinases. PAK also mediates polarized cytoskeletal changes induced by these
      GTPases. The recently identified PAK-interacting exchange factor (PIX) acts as a 
      guanine nucleotide exchange factor on Rac, and colocalizes with PAK in a focal
      complex, but little is known about the associated signaling cascades, including
      upstream activators of PIX. In this study, we show that one of the isoforms of
      PIX, alphaPIX, is activated by signaling cascades from the platelet-derived
      growth factor (PDGF) receptor and EphB2 receptor, and from integrin-induced
      signaling through phosphatidylinositol 3-kinase (PI3-kinase). alphaPIX is
      activated by forming a complex with these receptors either via association with
      PAK and Nck, or direct association with the p85 regulatory subunit of PI3-kinase.
      Synthetic phosphoinositide and membrane targeted PI3-kinase augmented the
      alphaPIX activity in vivo. In Xenopus, aggregates of mesodermal cells derived
      from embryos microinjected with alphaPIX significantly increased the peripheral
      spreading on fibronectin substrate in response to PDGF through PI3-kinase. These 
      results indicate that alphaPIX is activated by PI3-kinase, and is involved in the
      receptor mediated signaling leading to the activation of the kinase activity of
      PAK, and the migration of mesodermal cells on extracellular matrix.
FAU - Yoshii, S
AU  - Yoshii S
AD  - The First Department of Pathology, Hamamatsu University School of Medicine, 3600 
      Handa-cho, Hamamatsu, 431-3192 Japan.
FAU - Tanaka, M
AU  - Tanaka M
FAU - Otsuki, Y
AU  - Otsuki Y
FAU - Wang, D Y
AU  - Wang DY
FAU - Guo, R J
AU  - Guo RJ
FAU - Zhu, Y
AU  - Zhu Y
FAU - Takeda, R
AU  - Takeda R
FAU - Hanai, H
AU  - Hanai H
FAU - Kaneko, E
AU  - Kaneko E
FAU - Sugimura, H
AU  - Sugimura H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Fibronectins)
RN  - 0 (Guanine Nucleotide Exchange Factors)
RN  - 0 (Macromolecular Substances)
RN  - 0 (Nck protein)
RN  - 0 (Oncogene Proteins)
RN  - 0 (Protein Isoforms)
RN  - 0 (Rho Guanine Nucleotide Exchange Factors)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, EphB2)
RN  - EC 2.7.10.1 (Receptors, Platelet-Derived Growth Factor)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (p21-Activated Kinases)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - COS Cells
MH  - Cell Adhesion
MH  - Cell Cycle Proteins/*physiology
MH  - Cell Movement
MH  - Chlorocebus aethiops
MH  - Cytoskeleton/ultrastructure
MH  - Extracellular Matrix
MH  - Fibronectins
MH  - GTP Phosphohydrolases/physiology
MH  - *Guanine Nucleotide Exchange Factors
MH  - MAP Kinase Signaling System
MH  - Macromolecular Substances
MH  - Mesoderm/cytology
MH  - Microinjections
MH  - Models, Biological
MH  - Oncogene Proteins/physiology
MH  - Phosphatidylinositol 3-Kinases/*physiology
MH  - Phosphorylation
MH  - Protein Isoforms/*physiology
MH  - Protein Processing, Post-Translational
MH  - Protein Serine-Threonine Kinases/physiology
MH  - Receptor Protein-Tyrosine Kinases/physiology
MH  - Receptor, EphB2
MH  - Receptors, Platelet-Derived Growth Factor/physiology
MH  - Rho Guanine Nucleotide Exchange Factors
MH  - Signal Transduction/*physiology
MH  - Xenopus laevis/embryology
MH  - p21-Activated Kinases
MH  - src Homology Domains
EDAT- 1999/10/19 09:00
MHDA- 2000/10/18 11:01
CRDT- 1999/10/19 09:00
PHST- 1999/10/19 09:00 [pubmed]
PHST- 2000/10/18 11:01 [medline]
PHST- 1999/10/19 09:00 [entrez]
AID - 10.1038/sj.onc.1202936 [doi]
PST - ppublish
SO  - Oncogene. 1999 Oct 7;18(41):5680-90. doi: 10.1038/sj.onc.1202936.