Neonatal cerebral hypoxia-ischemia: involvement of FAK-dependent pathway.
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase thought to play a major role in transducing extracellular matrix (ECM)-derived survival signals into cells. Thus, modulation of FAK activity may affect the linkage between ECM and signaling cascade to which it is connected and may participate in a variety of pathological settings. In the present study, we investigated the effect of neonatal cerebral hypoxia-ischemia (HI) on levels and tyrosine phosphorylation of focal adhesion kinase and the interaction of this enzyme with Src protein tyrosine kinase and adapter protein p130Cas, involved in FAK-mediated signaling pathway. The total amount of focal adhesion kinase as well as its phosphorylated form declined substantially to about 50% of the control between 24 and 48 h after the insult. Concomitantly a decreased association of FAK with its investigated molecular partners, Src kinase and p130Cas protein has been observed. This early response to brain hypoxia-ischemia was attenuated during prolonged recovery with almost complete return to control values at 7 days. These data are indicative of an involvement of FAK-dependent signaling pathway in the evolution of HI-induced neuronal degeneration.
Zalewska
Teresa
T
NeuroRepair Department, Medical Research Institute, Polish Academy of Sciences, 5 Pawinskiego Str., 02-106 Warsaw, Poland. terezal@cmdik.pan.pl
Makarewicz
Dorota
D
Janik
Bernardetta
B
Ziemka-Nałecz
Małgorzata
M
D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D015153:Blotting, Western; D050719:Crk-Associated Substrate Protein / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000502:physiology*; D002534:Hypoxia, Brain / Q000201:enzymology / Q000473:pathology*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000502:physiology
D050719:Crk-Associated Substrate Protein; D014443:Tyrosine; D051417:Focal Adhesion Kinase 1; C496052:Ptk2 protein, rat; D019061:src-Family Kinases