Genetic evidence for a tyrosine kinase cascade preceding the mitogen- activated protein kinase cascade in vertebrate G protein signaling

Yong Wan, Kendra Bence, Akiko Hata, Tomohiro Kurosaki, Andre Veillette, Xin Yun Huang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

The signal transduction pathway from heterotrimeric G proteins to the mitogen-activated protein kinase (MAPK) cascade is best understood in the yeast mating pheromone response, in which a serine/threonine protein kinase (STE20) serves as the critical linking component. Little is known in metazoans on how G proteins and the MAPK cascade are coupled. Here we provide genetic and biochemical evidence that a tyrosine kinase cascade bridges G proteins and the MAPK pathway in vertebrate cells. Targeted deletion of tyrosine kinase Csk in avian B lymphoma cells blocks the stimulation of MAPK by G(q)-, but not G(i)-, coupled receptors. In cells deficient in Bruton's tyrosine kinase (Btk), G(i)-coupled receptors failed to activate MAPK, while G(q)-coupled receptor-mediated stimulation is unaffected. Taken together with our previous data on tyrosine kinases Lyn and Syk, the G(q)-coupled pathway requires tyrosine kinases Csk, Lyn, and Syk, while the G(i)-coupled pathway requires tyrosine kinases Btk and Syk to feed into the MAPK cascade in these cells. The central role of Syk is further strengthened by data showing that Syk can bind to purified Lyn, Csk, or Btk.

Original languageEnglish (US)
Pages (from-to)17209-17215
Number of pages7
JournalJournal of Biological Chemistry
Volume272
Issue number27
DOIs
StatePublished - Jul 4 1997

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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