Focal adhesion kinase (FAK) and proline-rich tyrosine kinase (PYK2) are two related non-receptor tyrosine kinases which are thought to play a role in transducing extracellular matrix (ECM)-derived survival signals into cells. The functions of FAK and PYK2 are linked to autophosphorylation of their specific tyrosine residues, Tyr-397 in FAK and Tyr-402 in PYK2, and then association with different signalling proteins which mediate activation of downstream targets such as ERK and JNK mitogen-activated kinase cascades. Thus, modulation of FAK as well as PYK2 autophosphorylation may affect several intracellular pathways and may participate in a variety of pathological settings. The present study provides a systematic investigation of the influence of experimental ischemia, induced by oxygen-glucose-deprivation, on the FAK- and PYK2-mediated signalling in organotypic hippocampal slice cultures. OGD induced primary down-regulation of FAK and PYK2 autophosphorylation (at Tyr 397 and Tyr 402, respectively) at 24-48 h of reoxygenation was accompanied by the diminution of phosphorylation/activation of Src and JNK. In contrast, the activity of Akt and ERK1/2 remained on the control level. It indicates that Akt kinase as well as ERK1/2 does not interfere with OGD-induced neuronal damage. The inhibition of the early step of FAK and PYK2 activation demonstrated by the decrease of tyrosine autophosphorylation may comprise an important portion of the response expressed by modulation of some coupled signal transduction pathways.
Keywords: Akt; FAK; MAPK; OGD; PYK2; Src.
Copyright © 2015 Elsevier B.V. All rights reserved.