Preserved phosphorylation of RET receptor protein in spinal motor neurons of patients with amyotrophic lateral sclerosis: an immunohistochemical study by a phosphorylation-specific antibody at tyrosine 1062

Ret oncoprotein is a functional receptor for the glial cell line-derived ne urotrophic factor (GDNF) family and it is expressed in motor neurons, playi ng an important role in the motor neuron function. In this study, we examin ed the expression of the phosphorylation state of tyrosine residue 1062 (Ty r-1062) of Ret in the spinal cords of amyotrophic lateral sclerosis (ALS), using the phosphorylation state specific antibody at Tyr-1062 of Ret. The i mmunohistochemical study demonstrated that Tyr-1062 of Ret was phosphorylat ed to variable extents in the surviving motor neurons of all the ALS as wel l as controls studied. This is the first report that the phosphorylation of Tyr-1062 occurred in neurons with nononcogenic type of Ret. The Ret-signal ing pathway by Tyr-1062 autophosphorylation is constitutively activated via the phosphatidylinositol 3-kinase and/or mitogen-activated protein kinase cascade for motoneuron survival even in the ALS motor neurons, supporting t he view that GDNF is a candidate for therapeutic approach to ALS. (C) 2001 Elsevier Science B.V.All rights reserved.