A requirement for Syk in the activation of the microtubule-associated protein kinase/phospholipase A2 pathway by FcεR1 is not shared by a G protein-coupled receptor

N. Hirasawa, A. Scharenberg, H. Yamamura, M. A. Beaven, J. P. Kinet

Research output: Contribution to journalArticlepeer-review

139 Citations (Scopus)

Abstract

Stimulation of the mast cell line, RBL-2H3, with antigen via the tetrameric (αβγ2) immunoglobulin E receptor (FcεR1) leads to the activation of cytosolic phospholipase A2 and the release of arachidonic acid. This pathway is dependent on the activation of the mitogen-activated protein (MAP) kinase. In this paper, we show that the MAP kinase/cytosolic phospholipase A2 pathway is linked to FcεR1 via the cytosolic tyrosine kinase, Syk, and that the GDP/GTP exchange factor, Vav, might be one candidate for accomplishing this link. Cross-linking of transmembrane chimeras containing the FcεR1γ motif, which is known to activate Syk, results in the tyrosine phosphorylation of Vav, activation of MAP kinase, and release of arachidonic acid. Cross-linking of chimeras containing the FcεR1β motif does not cause these events. Furthermore, stimulation of these events by antigen is enhanced by transient overexpression of a wild-type form of Syk and blocked by overexpression of a dominant negative form of Syk. By contrast, stimulation via the transfected, G protein-coupled, muscarinic m1 receptor is not influenced by either form of Syk and does not result in tyrosine phosphorylation of Vav. These data establish unequivocally that the two types of receptor are independently linked to the MAP kinase/cytosolic phospholipase A2 pathway and demonstrate the existence of the FcεR1-Syk- MAP kinase pathway.

Original languageEnglish
Pages (from-to)10960-10967
Number of pages8
JournalJournal of Biological Chemistry
Volume270
Issue number18
DOIs
Publication statusPublished - 1995
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'A requirement for Syk in the activation of the microtubule-associated protein kinase/phospholipase A<sub>2</sub> pathway by FcεR1 is not shared by a G protein-coupled receptor'. Together they form a unique fingerprint.

Cite this