Activation of the EphA2 tyrosine kinase stimulates the MAP/ERK kinase signaling cascade

Rebecca L. Pratt, Michael S. Kinch

Research output: Contribution to journalArticlepeer-review

119 Scopus citations


Intracellular signaling by receptor tyrosine kinases regulates many different aspects of cell behavior. Recent studies in our laboratory and others have demonstrated that the EphA2 receptor tyrosine kinase critically regulates tumor cell growth, migration and invasiveness. Although the cellular consequences of EphA2 signaling have been the focus of recent attention, the biochemical changes that are triggered by ligand-mediated activation of EphA2 remain largely unknown. Herein, we demonstrate that ligand stimulation of EphA2 promotes the nucleus translocation and phosphorylation of ERK kinases, followed by an increase in nuclear induction of the Elk-1 transcription factor. Ligand-mediated activation allows EphA2 to form a molecular complex with the SHC and GRB2 adaptor proteins. Specifically, we demonstrate that tyrosine phosphorylated EphA2 interacts with the PTB and SH2 domains of SHC. We also show that the interaction of EphA2 with GRB2 is indirect and mediated by SHC and that this complex is necessary for EphA2-mediated activation of ERK kinases. These studies provide a novel mechanism to demonstrate how EphA2 can convey information from the cell exterior to the nucleus.

Original languageEnglish
Pages (from-to)7690-7699
Number of pages10
Issue number50
StatePublished - Oct 31 2002


  • Eck
  • Eph kinase
  • Signal transduction


Dive into the research topics of 'Activation of the EphA2 tyrosine kinase stimulates the MAP/ERK kinase signaling cascade'. Together they form a unique fingerprint.

Cite this