c-Src is a PDZ interaction partner and substrate of the E3 ubiquitin ligase Ligand-of-Numb protein X1

FEBS Lett. 2007 Oct 30;581(26):5131-6. doi: 10.1016/j.febslet.2007.09.062. Epub 2007 Oct 8.


The very C-terminus of c-Src is a ligand for PDZ domains. In a screen for PDZ domains that interact with c-Src, we identified one of the PDZ domains of the Ligand-of-Numb protein X1 (LNX1), a multiple PDZ domain scaffold and RING type E3 ubiquitin ligase. We demonstrate that the interaction of c-Src with LNX1 depends on the C-terminal PDZ ligand of c-Src. Furthermore, we show that c-Src phosphorylates LNX1. Moreover, c-Src itself is ubiquitinated by LNX1, suggesting an interdependent regulation of c-Src and LNX1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CSK Tyrosine-Protein Kinase
  • Cell Line
  • Humans
  • Ligands
  • PDZ Domains*
  • Phosphorylation
  • Protein Interaction Mapping
  • Protein-Tyrosine Kinases / analysis
  • Protein-Tyrosine Kinases / metabolism*
  • Substrate Specificity
  • Ubiquitin / metabolism
  • Ubiquitin-Protein Ligases / analysis
  • Ubiquitin-Protein Ligases / metabolism*
  • src-Family Kinases


  • Ligands
  • Ubiquitin
  • LNX1 protein, human
  • Ubiquitin-Protein Ligases
  • Protein-Tyrosine Kinases
  • CSK Tyrosine-Protein Kinase
  • src-Family Kinases
  • CSK protein, human