Association of the abl tyrosine kinase with the Trk nerve growth factor receptor

Nerve growth factor (NGF) initiates the majority of its biological effects by promoting the dimerization and activation of the tyrosine kinase recepto r TrkA. In addition to rapid increases in the phosphorylation of phosphatid ylinositol 3'-kinase (PI 3-kinase) and phospholipase C-gamma and increased ras activity, phosphorylation of c-Crk and paxillin proteins has been obser ved upon TrkA activation. The c-Abl tyrosine kinase is involved in the cont rol of the axonal cytoskeleton and is known to interact with c-Crk proteins . Here we have tested the possibility that TrkA receptors might form an ass ociation with the c-Abl protein. After transfection in 293T cells, TrkA and c-Abl kinases could be coimmunoprecipitated. This interaction did not requ ire TrkA receptors to be autophosphorylated. Mapping analysis indicated tha t the region of c-Abl association was confined to the juxtamembrane region of TrkA. The interaction of c-Abl with TrkA was also observed in differenti ated pheochromocytoma PC12 cells. These results suggest that c-Abl may be r ecruited to the NGF receptor complex and be involved in regulating specific phosphorylation events that occur during neuronal differentiation. (C) 200 0 Wiley-Liss, Inc.