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.