Protein kinase signaling cascades in CNS trauma.

Advances in our understanding of the signaling pathways and cellular functions regulated by protein kinase cascades have paved the way to study their role in the response of brain and spinal cord to traumatic injury. Mechanical forces imparted by trauma stimulate mitogen-activated protein kinases and protein kinase B/Akt as well as cause changes in the state of phosphorylation of glycogen synthase kinase-3beta. Extracellular ATP released by mechanical strain stimulates P2 purinergic receptors that are coupled to these protein kinase signaling pathways. These kinases regulate gene expression, cell survival, proliferation, differentiation, growth arrest, and apoptosis, thereby affecting cell fate, repair and plasticity after trauma. Elucidation of the molecular responses of protein kinase cascades to mechanical strain and the genes regulated by these signaling pathways may lead to therapeutic opportunities to minimize losses in motor skills and cognitive function caused by trauma to the central nervous system.