PARG1, a protein-tyrosine phosphatase-associated RhoGAP, as a putative Rap2 effector.
Rap2 belongs to the Ras family of small GTP-binding proteins, but its specific signaling role is unclear. By yeast two-hybrid screening, we have found that the Caenorhabditis elegans ortholog of Rap2 interacts with a protein containing a Rho-GTPase-activating protein (RhoGAP) domain, ZK669.1a, whose human ortholog PARG1 exhibits RhoGAP activity in vitro. ZK669.1a and PARG1 share a homology region with previously unknown function, designated the ZK669.1a and PARG1 homology (ZPH) region. Here we show that the ZPH region of PARG1 mediates interaction with Rap2. PARG1 interacted with Rap2 in a GTP-dependent manner but not with Ras or Rap1. We also show that PARG1 and its mutant lacking the ZPH region induce typical cytoskeletal changes for Rho inactivation in fibroblasts. Rap2 suppressed this in vivo action of PARG1 but not that of the mutant PARG1. These results suggest that PARG1 is a putative specific effector of Rap2 to regulate Rho.
Myagmar
Bat-Erdene
BE
Division of Cell Biology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa 903-0215, Japan.
Umikawa
Masato
M
Asato
Tsuyoshi
T
Taira
Kiyohito
K
Oshiro
Minoru
M
Hino
Asako
A
Takei
Kimiko
K
Uezato
Hiroshi
H
Kariya
Ken-ichi
K
D000818:Animals; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D041681:NIH 3T3 Cells; D011485:Protein Binding; D025941:Protein Interaction Mapping; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D020798:Two-Hybrid System Techniques; D020668:rap GTP-Binding Proteins / Q000378:metabolism*
C500429:ARHGAP29 protein, human; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D020690:GTPase-Activating Proteins; D047908:Intracellular Signaling Peptides and Proteins; C486394:Rap2ip protein, mouse; C516742:PTPN13 protein, human; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases; C516743:Ptpn13 protein, mouse; D020668:rap GTP-Binding Proteins