TY - JOUR T1 - Role of Integrin-Linked Kinase in Nerve Growth Factor-Stimulated Neurite Outgrowth JF - The Journal of Neuroscience JO - J. Neurosci. SP - 1638 LP - 1648 DO - 10.1523/JNEUROSCI.23-05-01638.2003 VL - 23 IS - 5 AU - Julia Mills AU - Murat Digicaylioglu AU - Arthur T. Legg AU - Clint E. Young AU - Sean S. Young AU - Alasdair M. Barr AU - Lauren Fletcher AU - Timothy P. O'Connor AU - Shoukat Dedhar Y1 - 2003/03/01 UR - http://www.jneurosci.org/content/23/5/1638.abstract N2 - The role of integrin-linked kinase (ILK), a kinase that is involved in various cellular processes, including adhesion and migration, has not been studied in primary neurons. Using mRNA dot blot and Western blot analysis of ILK in rat and human brain tissue, we found that ILK is expressed in various regions of the CNS. Immunohistochemical and immunocytochemical techniques revealed granular ILK staining that is enriched in neurons and colocalizes with the β1 integrin subunit. The role of ILK in neurite growth promotion by NGF was studied in rat pheochromocytoma cells and dorsal root ganglion neurons using a pharmacological inhibitor of ILK (KP-392) or after overexpression of dominant-negative ILK (ILK-DN). Both molecular and pharmacological inhibition of ILK activity significantly reduced NGF-induced neurite outgrowth. Survival assays indicate that KP-392-induced suppression of neurite outgrowth occurred in the absence of cell death. ILK kinase activity was stimulated by NGF. NGF-mediated stimulation of phosphorylation of both AKT and the Tau kinase glycogen synthase kinase-3 (GSK-3) was inhibited in the presence of KP-392 and after overexpression of ILK-DN. Consequently, ILK inhibition resulted in an increase in the hyperphosphorylation ofTau, a substrate of GSK-3. Together these findings indicate that ILK is an important effector in NGF-mediated neurite outgrowth. ER -