PMID:15545601

Citation	Aiba, Y, Oh-hora, M, Kiyonaka, S, Kimura, Y, Hijikata, A, Mori, Y and Kurosaki, T (2004) Activation of RasGRP3 by phosphorylation of Thr-133 is required for B cell receptor-mediated Ras activation. Proc. Natl. Acad. Sci. U.S.A. 101:16612-7
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-gamma2 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.
Links	PubMed PMC528733 Online version:10.1073/pnas.0407468101
Keywords	Amino Acid Sequence; Animals; Cell Line; Chickens; Cross-Linking Reagents; Guanine Nucleotide Exchange Factors/chemistry; Guanine Nucleotide Exchange Factors/genetics; Guanine Nucleotide Exchange Factors/metabolism; Humans; Models, Molecular; Mutation; Phospholipase C gamma; Phosphorylation; Protein Conformation; Protein Kinase C/metabolism; Receptors, Antigen, B-Cell/metabolism; Recombinant Proteins/chemistry; Recombinant Proteins/genetics; Recombinant Proteins/metabolism; Sequence Homology, Amino Acid; Signal Transduction; Static Electricity; Threonine/chemistry; Type C Phospholipases/metabolism; ras Proteins/metabolism
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