Ras-independent activation of ERK signaling via the Torso receptor tyrosine kinase is mediated by Rap1

Snigdha Mishra, Sarah M. Smolik, Michael Forte, Philip Stork

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

In Drosophila embryos, the Torso receptor tyrosine kinase (RTK) activates the small G protein Ras (D-Ras1) and the protein kinase Raf (D-Raf) to activate ERK to direct differentiation of terminal structures [1]. However, genetic studies have demonstrated that Torso, and by extension other RTKs, can activate Raf and ERK independently of Ras [2]. In mammalian cells, the small G protein Rap1 has been proposed to couple RTKs to ERKs. However, the ability of Rap1 to activate ERKs remains controversial, in part because direct genetic evidence supporting this hypothesis is lacking. Here, we present biochemical and genetic evidence that D-Rap1, the Drosophila homolog of Rap1, can activate D-Raf and ERK. We show that D-Rap1 binds D-Raf and activates ERKs in a GTP- and D-Raf-dependent manner. Targeted disruption of D-Rap1 expression decreased both Torso-dependent ERK activation and the ERK-dependent expression of the zygotic genes tailless and huckebein to levels similar to those achieved in D-Ras1 null embryos. Furthermore, combined deficiencies of D-Ras1 and D-Rap1 completely abolished expression of these genes, mimicking the phenotype observed in embryos lacking D-Raf. These studies provide the first direct genetic evidence of Rap1-mediated activation of the MAP kinase cascade in eukaryotic organisms.

Original languageEnglish (US)
Pages (from-to)366-370
Number of pages5
JournalCurrent Biology
Volume15
Issue number4
DOIs
StatePublished - Feb 22 2005

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torso
Torso
Monomeric GTP-Binding Proteins
Receptor Protein-Tyrosine Kinases
mitogen-activated protein kinase
tyrosine
phosphotransferases (kinases)
Embryonic Structures
Genes
Chemical activation
receptors
Drosophila
Guanosine Triphosphate
Protein Kinases
Gene Expression
Phosphotransferases
MAP Kinase Signaling System
Cells
Molecular Biology
Phenotype

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

Ras-independent activation of ERK signaling via the Torso receptor tyrosine kinase is mediated by Rap1. / Mishra, Snigdha; Smolik, Sarah M.; Forte, Michael; Stork, Philip.

In: Current Biology, Vol. 15, No. 4, 22.02.2005, p. 366-370.

Research output: Contribution to journalArticle

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