Activation of the ERK/MAPK pathway by an isoform of rap1GAP associated with Gαi

Naoki Mochizuki, Yusuke Ohba, Etsuko Kiyokawa, Takeshi Kurata, Takeshi Murakami, Takefumi Ozaki, Akira Kitabatake, Kazuo Nagashima and Michiyuki Matsuda ()
Additional contact information
Naoki Mochizuki: Research Institute, International Medical Center of Japan
Yusuke Ohba: Research Institute, International Medical Center of Japan
Etsuko Kiyokawa: National Institute of Infectious Diseases
Takeshi Kurata: National Institute of Infectious Diseases
Takeshi Murakami: Departments of Cardiovascular Medicine
Takefumi Ozaki: Departments of Cardiovascular Medicine
Akira Kitabatake: Departments of Cardiovascular Medicine
Kazuo Nagashima: Pathology, Hokkaido University School of Medicine
Michiyuki Matsuda: Research Institute, International Medical Center of Japan

Nature, 1999, vol. 400, issue 6747, 891-894

Abstract: Abstract Many receptors for neuropeptides and hormones are coupled with the heterotrimeric Gi protein, which activates the p42/44 mitogen-activated protein kinase (ERK/MAPK) cascade through both the α- and βγ-subunits of Gi (1–3). The βγ-subunit activates the ERK/MAPK cascade through tyrosine kinase4,5,6. Constitutively active Gαi2 (gip2) isolated from adrenal and ovarian tumours7,8 transforms Rat-1 fibroblasts and also activates the ERK/MAPK cascade by an unknown mechanism9,10. The ERK/MAPK pathway is activated by Ras, and is inhibited when the low-molecular-mass GTP-binding protein Rap1 antagonizes Ras function11. Here we show that a novel isoform of Rap1 GTPase-activating protein, called rap1GAPII, binds specifically to the α-subunits of the Gi family of heterotrimeric G-proteins. Stimulation of the Gi-coupled m2-muscarinic receptor translocates rap1GAPII from the cytosol to the membrane and decreases the amount of GTP-bound Rap1. This decrease in GTP-bound Rap1 activates ERK/MAPK. Thus, the α-subunit of Gi activates the Ras-ERK/MAPK mitogenic pathway by membrane recruitment of rap1GAPII and reduction of GTP-bound Rap1.

Date: 1999
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/23738 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:400:y:1999:i:6747:d:10.1038_23738

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/23738

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().