c-Src is a PDZ interaction partner and substrate of the E3 ubiquitin ligase Ligand-of-Numb protein X1.
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.
Weiss
Andreas
A
Institute of Medical Virology, University of Zurich, Gloriastrasse 30, 8006 Zurich, Switzerland. andreas.weiss@usz.ch
Baumgartner
Martin
M
Radziwill
Gerald
G
Dennler
Julia
J
Moelling
Karin
K
D000081247:CSK Tyrosine-Protein Kinase; D002460:Cell Line; D006801:Humans; D008024:Ligands; D054731:PDZ Domains; D010766:Phosphorylation; D025941:Protein Interaction Mapping; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000378:metabolism*; D013379:Substrate Specificity; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000032:analysis / Q000378:metabolism*; D019061:src-Family Kinases
D008024:Ligands; D025801:Ubiquitin; C484733:LNX1 protein, human; D044767:Ubiquitin-Protein Ligases; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human