Activation of RasGRP3 by phosphorylation of Thr-133 is required for B cell receptor-mediated Ras activation

Yuichi Aiba, Masatsugu Oh-Hora, Shigeki Kiyonaka, Yayoi Kimura, Atsushi Hijikata, Yasuo Mori, Tomohiro Kurosaki

Research output: Contribution to journalArticlepeer-review

66 Citations (Scopus)

Abstract

The Ras signaling pathway plays a critical role in B lymphocyte development and activation, but its activation mechanism has not been well understood. At least one mode of Ras regulation in B cells involves a Ras-guanyl nucleotide exchange factor, RasGRP3. We demonstrate here that RasGRP3 undergoes phosphorylation at Thr-133 upon B cell receptor cross-linking, thereby resulting in its activation. Deletion of phospholipase C-γ2 or pharmacological interference with conventional PKCs resulted in marked reduction in both Thr-133 phosphorylation and Ras activation. Moreover, mutation of Thr-133 in RasGRP3 alone severely impaired its ability to activate Ras in B cell receptor signaling. Hence, our data suggest that PKC, after being activated by diacylglycerol, phosphorylates RasGRP3, thereby contributing to its full activation.

Original languageEnglish
Pages (from-to)16612-16617
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number47
DOIs
Publication statusPublished - Nov 23 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

Fingerprint

Dive into the research topics of 'Activation of RasGRP3 by phosphorylation of Thr-133 is required for B cell receptor-mediated Ras activation'. Together they form a unique fingerprint.

Cite this