Genetic evidence for a tyrosine kinase cascade preceding the mitogen-activated protein kinase cascade in vertebrate G protein signaling Journal Article
| Authors: | Wan, Y.; Bence, K.; Hata, A.; Kurosaki, T.; Veillette, A.; Huang, X. Y. |
| Article Title: | Genetic evidence for a tyrosine kinase cascade preceding the mitogen-activated protein kinase cascade in vertebrate G protein signaling |
| 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. |
| Keywords: | signal transduction; mitogen activated protein kinase; controlled study; nonhuman; binding affinity; animal cell; animals; gtp-binding proteins; tumor cells, cultured; protein serine threonine kinase; protein tyrosine kinase; animalia; vertebrata; aves; intracellular signaling peptides and proteins; immunoprecipitation; immunoblotting; models, genetic; binding sites; protein-tyrosine kinases; receptor; src-family kinases; guanine nucleotide binding protein; autoradiography; enzyme precursors; polyacrylamide gel electrophoresis; metazoa; ca(2+)-calmodulin dependent protein kinase; priority journal; article; src homology domains; pheromone; fowl; galliformes |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 272 |
| Issue: | 27 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 1997-07-04 |
| Start Page: | 17209 |
| End Page: | 17215 |
| Language: | English |
| DOI: | 10.1074/jbc.272.27.17209 |
| PUBMED: | 9202044 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 17 March 2017 -- Source: Scopus |
