ABSTRACT
Pyk2(Proline-rich tyrosine kinase 2) is an important member of focal adhesion kinase family. Pyk2 is highly ex-pressed in the central nervous system and the hematopoietic sys-tem . Pyk 2 can trigger a variety of SH 2 domain-containing pro- teins to phosphorylate their substrates, thus it can participate in the regulations including ion channel activation, stress response, cell adhesion, cytoskeleton reorganization, vesicle transport and so on. Through the regulations above, the ability of cell migra-tion, survival, proliferation changes accordingly, suggesting that Pyk2 in many important regulatory processes may become a tar-get for clinical effects. Current drug development for Pyk2 main- ly focuses on cancer, osteoporosis and immune response. This review illustrates the domain structure, regulatory mechanisms, potential drug targets, and the drug development of Pyk2 based on the above three fields, which will provide a theoretical basis for clinical treatment.
ABSTRACT
Objective To investigate and evaluate the changes of PYK2 expression in hippocampal neurons and microglial cells in Kainate acid-induced status epilepticus. Methods Kainate acid-induced status epilepticus was established in rats, and by using immunostaining, changes of PYK2 expression in hippocampal neurons and microglial cells was investigated. Results Expression of PYK2 in hippocampal pyramidal neurons was markedly decreased after kainate acid-induced status epilepticus. However, 24h after the epileptic onset, a pronounced up-regulation of PYK2 and phosphor-PYK2 immunoreactivities were evident in amoeboid microglial cells. The upregulation of PYK2 and phosphor-PYK2 was in accordance with the morphological changes of the activated microglial cells. Conclusion PYK2 was activated in microglial cells after seizure. Furthermore, the activation of PYK2 in microglial cells after seizure might be related to the morphological and behavioral changes of microglial cells after activation.
ABSTRACT
Objective To investigate and evaluate the changes of phospho PYK2 and phospho p38MAPK expression in neurons after focal cerebral ischemia. Methods Focal ischemia reperfusion model was established in rats, and by using immunostaining, the changes of phospho PYK2 and phospho p38MAPK expression in neurons was observed. Results Faint phospho PYK2 and phospho p38MAPK immunoreactivity were revealed in normal cortical neurons. Fifteen minutes after the ischemia onset, a pronounced upregulation of phospho PYK2 and phospho p38MAPK immunoreactivities were evident in these ischemia attacked neurons. The immunoreactivities of phospho PYK2 and phospho p38MAPK reached its peak at 30min after ischemia, and decreased 60min after ischemia. Conclusion Cerebral ischemia was able to induce neuronal PYK2 phosphorylation. The activation of PYK2 might link ischemia attack to the p38MAPK signaling pathway to initiate the neuronal response to the stress stimuli