IndraLab

"We report the identification of PTPRK and PTPRJ (density-enhanced phosphatase-1 [DEP-1]) as EGFR-targeting phosphatases. DEP-1 is a tumor suppressor that dephosphorylates and thereby stabilizes EGFR by hampering its ability to associate with the CBL-GRB2 ubiquitin ligase complex|By employing commercially available antibodies, which are supposed to recognize specific tyrosine phosphorylation sites of EGFR, we found that depletion of endogenous DEP-1 nonselectively increased receptor phosphorylation, affecting all three sites we analyzed (tyrosines 1045, 1068, and 1173"

"Initially, an autophosphorylation reaction creates docking sites for several signaling proteins, including a Cbl binding site at tyrosine 1045 of EGFR. Second, EGFR trans-phosphorylates Cbl at a linker domain, which activates an associated ubiquitin ligase activity."