Activation of Pyk2/RAFTK induces tyrosine phosphorylation of alpha-synuclein via Src-family kinases.
alpha-Synuclein (alpha S) is a neuronal protein that has been implicated in the pathogenesis of Parkinson's disease. The present report demonstrates that the protein tyrosine kinase Pyk2/RAFTK is involved in cell stress-induced tyrosine phosphorylation of alpha S. Hyperosmotic stress induced tyrosine phosphorylation of alpha S via Pyk2/RAFTK at tyrosine residue 125. Pyk2/RAFTK-mediated phosphorylation of alpha S was primarily achieved with Src-family kinases. In addition, osmotic stress-induced phosphorylation of alpha S was dependent on Pyk2/RAFTK activation. Accordingly, such results indicate that Pyk2/RAFTK lies upstream of Src-family kinases in the signaling cascade by which osmotic stress induces tyrosine phosphorylation of alpha S.
Nakamura
Takeshi
T
Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences, Japan.
Yamashita
Hiroshi
H
Nagano
Yoshito
Y
Takahashi
Tetsuya
T
Avraham
Shalom
S
Avraham
Hava
H
Matsumoto
Masayasu
M
Nakamura
Shigenobu
S
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004789:Enzyme Activation; D051418:Focal Adhesion Kinase 2; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000235:genetics / Q000378:metabolism*; D051843:Synucleins; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism*; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D051843:Synucleins; D051844:alpha-Synuclein; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051418:Focal Adhesion Kinase 2; D016392:Proto-Oncogene Proteins pp60(c-src)