Tyrosine kinases in activation of the MAP kinase cascade by G-protein-coupled receptors

Yong Wan, Tomohiro Kurosaki*, Xin Yun Huang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

251 Scopus citations

Abstract

The mitogen-activated protein kinase (MAPK) signalling cascade is a prominent cellular pathway used by many growth factors, hormones and neurotransmitters to regulate physiological responses. Although activation of the MAPK pathway by receptors with tyrosine kinase activity is well defined, the mechanism used by heterotrimeric G-protein-coupled receptors to activate this pathway is less clear. Here we show that in cells deficient in the Src-related tyrosine kinase Lyn, stimulation of MAPK kinase and MAPK by G(q)-coupled m1 muscarinic acetylcholine receptors (mAChR) is blocked, whereas G(i)-coupled m2 mAChR-mediated stimulation is unaffected. In cells deficient in the tyrosine kinase Syk, both m1 and m2 mAChRs failed to stimulate MAPK kinase and MAPK. This result indicates that Syk is essential for the G(i)-coupled pathway and that Lyn and Syk are necessary for the G(q)-coupled pathway.

Original languageEnglish (US)
Pages (from-to)541-544
Number of pages4
JournalNature
Volume380
Issue number6574
DOIs
StatePublished - Apr 11 1996

ASJC Scopus subject areas

  • General

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