Direct interaction of nerve growth factor receptor, TrkA, with non-receptor tyrosine kinase, c-Abl, through the activation loop.
The nerve growth factor receptor, TrkA, is essential for the survival and differentiation of neurons in the central and peripheral nervous systems. To understand the molecular principles underlying this differentiation step, we employed a yeast two-hybrid screening protocol using human TrkA as bait. We isolated c-Abl as a TrkA-interacting protein, in addition to known proteins such as phospholipase Cgamma and SH2-B. This interaction was confirmed by an in vitro binding assay using glutathione S-tranferase-Abl fusion protein. Furthermore, we show here that c-Abl binds to phosphotyrosine residue(s) in the kinase activation loop of TrkA.
Koch
A
A
Institut für Biochemie, OE 4310, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, 30623, Hannover, Germany.
Mancini
A
A
Stefan
M
M
Niedenthal
R
R
Niemann
H
H
Tamura
T
T
D048868:Adaptor Proteins, Signal Transducing; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics / Q000302:isolation & purification; D002454:Cell Differentiation; D004789:Enzyme Activation; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000302:isolation & purification; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051966:Phospholipase C gamma; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*; D020917:Receptor, trkA / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D010738:Type C Phospholipases / Q000235:genetics / Q000302:isolation & purification; D015003:Yeasts
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D007527:Isoenzymes; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; C518910:SH2B1 protein, human; D019000:Phosphotyrosine; D020917:Receptor, trkA; D016315:Proto-Oncogene Proteins c-abl; D010738:Type C Phospholipases; D051966:Phospholipase C gamma