IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-32541-4.html
   My bibliography  Save this article

SH3 domain regulation of RhoGAP activity: Crosstalk between p120RasGAP and DLC1 RhoGAP

Author

Listed:
  • Jocelyn E. Chau

    (Yale University)

  • Kimberly J. Vish

    (Yale University
    Yale University)

  • Titus J. Boggon

    (Yale University
    Yale University)

  • Amy L. Stiegler

    (Yale University)

Abstract

RhoGAP proteins are key regulators of Rho family GTPases and influence a variety of cellular processes, including cell migration, adhesion, and cytokinesis. These GTPase activating proteins (GAPs) downregulate Rho signaling by binding and enhancing the intrinsic GTPase activity of Rho proteins. Deleted in liver cancer 1 (DLC1) is a tumor suppressor and ubiquitously expressed RhoGAP protein; its activity is regulated in part by binding p120RasGAP, a GAP protein for the Ras GTPases. In this study, we report the co-crystal structure of the p120RasGAP SH3 domain bound directly to DLC1 RhoGAP, at a site partially overlapping the RhoA binding site and impinging on the catalytic arginine finger. We demonstrate biochemically that mutation of this interface relieves inhibition of RhoGAP activity by the SH3 domain. These results reveal the mechanism for inhibition of DLC1 RhoGAP activity by p120RasGAP and demonstrate the molecular basis for direct SH3 domain modulation of GAP activity.

Suggested Citation

  • Jocelyn E. Chau & Kimberly J. Vish & Titus J. Boggon & Amy L. Stiegler, 2022. "SH3 domain regulation of RhoGAP activity: Crosstalk between p120RasGAP and DLC1 RhoGAP," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32541-4
    DOI: 10.1038/s41467-022-32541-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-32541-4
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-32541-4?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Sandrine Etienne-Manneville & Alan Hall, 2002. "Rho GTPases in cell biology," Nature, Nature, vol. 420(6916), pages 629-635, December.
    2. Katrin Rittinger & Philip A. Walker & John F. Eccleston & Stephen J. Smerdon & Steven J. Gamblin, 1997. "Structure at 1.65 Å of RhoA and its GTPase-activating protein in complex with a transition-state analogue," Nature, Nature, vol. 389(6652), pages 758-762, October.
    3. Tracey Barrett & Bing Xiao & Eleanor J. Dodson & Guy Dodson & Steven B. Ludbrook & Kurshid Nurmahomed & Steven J. Gamblin & Andrea Musacchio & Stephen J. Smerdon & John F. Eccleston, 1997. "The structure of the GTPase-activating domain from p50rhoGAP," Nature, Nature, vol. 385(6615), pages 458-461, January.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Siqi Li & Kun Li & Kang Wang & Haoyuan Yu & Xiangyang Wang & Mengchen Shi & Zhixing Liang & Zhou Yang & Yongwei Hu & Yang Li & Wei Liu & Hua Li & Shuqun Cheng & Linsen Ye & Yang Yang, 2023. "Low-dose radiotherapy combined with dual PD-L1 and VEGFA blockade elicits antitumor response in hepatocellular carcinoma mediated by activated intratumoral CD8+ exhausted-like T cells," Nature Communications, Nature, vol. 14(1), pages 1-21, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Yuan Lin & Theresa A. Ramelot & Simge Senyuz & Attila Gursoy & Hyunbum Jang & Ruth Nussinov & Ozlem Keskin & Yi Zheng, 2024. "Tumor-derived RHOA mutants interact with effectors in the GDP-bound state," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Limei Wu & Srinivas Chatla & Qiqi Lin & Fabliha Ahmed Chowdhury & Werner Geldenhuys & Wei Du, 2021. "Quinacrine-CASIN combination overcomes chemoresistance in human acute lymphoid leukemia," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    3. Gabriela Casanova-Sepúlveda & Joel A. Sexton & Benjamin E. Turk & Titus J. Boggon, 2023. "Autoregulation of the LIM kinases by their PDZ domain," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    4. Cummings, F.W, 2004. "A model of morphogenesis," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 339(3), pages 531-547.
    5. Steffen Nørgaard & Shuer Deng & Wei Cao & Roger Pocock, 2018. "Distinct CED-10/Rac1 domains confer context-specific functions in development," PLOS Genetics, Public Library of Science, vol. 14(9), pages 1-24, September.
    6. Rashmi Priya & Guillermo A Gomez & Srikanth Budnar & Bipul R Acharya & Andras Czirok & Alpha S Yap & Zoltan Neufeld, 2017. "Bistable front dynamics in a contractile medium: Travelling wave fronts and cortical advection define stable zones of RhoA signaling at epithelial adherens junctions," PLOS Computational Biology, Public Library of Science, vol. 13(3), pages 1-19, March.
    7. Yasuo Takashima & Atsushi Kawaguchi & Junya Fukai & Yasuo Iwadate & Koji Kajiwara & Hiroaki Hondoh & Ryuya Yamanaka, 2021. "Survival prediction based on the gene expression associated with cancer morphology and microenvironment in primary central nervous system lymphoma," PLOS ONE, Public Library of Science, vol. 16(6), pages 1-14, June.
    8. Serena Petracchini & Daniel Hamaoui & Anne Doye & Atef Asnacios & Florian Fage & Elisa Vitiello & Martial Balland & Sebastien Janel & Frank Lafont & Mukund Gupta & Benoit Ladoux & Jerôme Gilleron & Te, 2022. "Optineurin links Hace1-dependent Rac ubiquitylation to integrin-mediated mechanotransduction to control bacterial invasion and cell division," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    9. Juan Manuel Ortiz-Sanchez & Sara E Nichols & Jacqueline Sayyah & Joan Heller Brown & J Andrew McCammon & Barry J Grant, 2012. "Identification of Potential Small Molecule Binding Pockets on Rho Family GTPases," PLOS ONE, Public Library of Science, vol. 7(7), pages 1-13, July.
    10. Guillaume Serwe & David Kachaner & Jessica Gagnon & Cédric Plutoni & Driss Lajoie & Eloïse Duramé & Malha Sahmi & Damien Garrido & Martin Lefrançois & Geneviève Arseneault & Marc K. Saba-El-Leil & Syl, 2023. "CNK2 promotes cancer cell motility by mediating ARF6 activation downstream of AXL signalling," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    11. Luís António Menezes Carreira & Dobromir Szadkowski & Stefano Lometto & Georg. K. A. Hochberg & Lotte Søgaard-Andersen, 2023. "Molecular basis and design principles of switchable front-rear polarity and directional migration in Myxococcus xanthus," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    12. Annmary Paul Erinjeri & Xunyan Wang & Rhianna Williams & Riccardo Zenezini Chiozzi & Konstantinos Thalassinos & Johnathan Labbadia, 2024. "HSF-1 promotes longevity through ubiquilin-1-dependent mitochondrial network remodelling," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32541-4. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.