Altered association of protein tyrosine kinases with postsynaptic densities after transient cerebral ischemia in the rat brain.
Transient cerebral ischemia results in an increase in the tyrosine phosphorylation of proteins associated with postsynaptic densities (PSDs). The authors investigated the possible mechanisms behind this increase by analyzing isolated PSDs for protein tyrosine kinase activity and for the presence of specific tyrosine kinases. Transient (15 minutes) global ischemia was produced in adult rats by four-vessel occlusion, and PSDs were isolated immediately after ischemia or after 20 minutes or 6 hours of reperfusion. Tyrosine phosphorylation of several PSD proteins, including the N-methyl-D-aspartate (NMDA) receptor subunits NR2A and NR2B, was enhanced relative to shams after 20 minutes of reperfusion and underwent a further increase between 20 minutes and 6 hours. The ability of intrinsic PSD tyrosine kinase to phosphorylate PSD proteins, including the NMDA receptor, increased threefold after ischemia. Whereas PSD-associated proline-rich tyrosine kinase 2 (PYK2) and gp145TrkB were elevated immediately after the ischemic event, increases in Src and Fyn were not apparent until 6 hours of reperfusion. The level of PSD-associated pp125FAK decreased after ischemia. The results demonstrate that ischemia results in selective changes in the association of protein tyrosine kinases with the PSD which may account for ischemia-induced increases in the tyrosine phosphorylation of PSD proteins.
Cheung
H H
HH
Division of Life Sciences, University of Toronto at Scarborough, Ontario, Canada.
Takagi
N
N
Teves
L
L
Logan
R
R
Wallace
M C
MC
Gurd
J W
JW
D000818:Animals; D001921:Brain / Q000201:enzymology*; D003840:Deoxycholic Acid / Q000494:pharmacology; D002546:Ischemic Attack, Transient / Q000201:enzymology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013569:Synapses / Q000201:enzymology*; D013574:Synaptosomes / Q000201:enzymology; D014443:Tyrosine / Q000378:metabolism
D009419:Nerve Tissue Proteins; D003840:Deoxycholic Acid; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases