c-Cbl binds to tyrosine-phosphorylated neurotrophin receptor p75 and induces its ubiquitination.
The p75 neurotrophin receptor (p75NTR) has dual functions in cell survival and cell death but its intracellular signalling pathways are not understood. Here we describe that in rat brain and in pervanadate-stimulated PCNA and HEK293 cells p75NTR is phosphorylated at a single tyrosine residue within the cytosolic C-terminus. Phosphorylated tyrosine 308 constitutes a binding site for the ubiquitin ligase c-Cbl. This interaction is a prerequisite for ubiquitination of p75NTR. Our data suggest a c-Cbl-dependent ubiquitination of p75NTR involved in the regulation of p75NTR signalling.
Ohrt
Thomas
T
Institute for Biophysics, University of Technology, 01307 Dresden, Germany.
Mancini
Annalisa
A
Tamura
Teruko
T
Niedenthal
Rainer
R
D000595:Amino Acid Sequence / Q000502:physiology; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D006801:Humans; D010766:Phosphorylation; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050721:Proto-Oncogene Proteins c-cbl; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D014638:Vanadates / Q000494:pharmacology
D011518:Proto-Oncogene Proteins; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D025801:Ubiquitin; C076715:pervanadate; D014638:Vanadates; D014443:Tyrosine; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; C067419:CBL protein, human