RGD Reference Report - Role of integrin-linked kinase in nerve growth factor-stimulated neurite outgrowth. - Rat Genome Database

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Role of integrin-linked kinase in nerve growth factor-stimulated neurite outgrowth.

Authors: Mills, J  Digicaylioglu, M  Legg, AT  Young, CE  Young, SS  Barr, AM  Fletcher, L  O'Connor, TP  Dedhar, S 
Citation: Mills J, etal., J Neurosci. 2003 Mar 1;23(5):1638-48.
RGD ID: 2302091
Pubmed: PMID:12629168   (View Abstract at PubMed)
PMCID: PMC6741947   (View Article at PubMed Central)

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 beta1 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 of Tau, a substrate of GSK-3. Together these findings indicate that ILK is an important effector in NGF-mediated neurite outgrowth.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
integrin-mediated signaling pathway  IMP 2302091 RGD 
negative regulation of neuron apoptotic process  IMP 2302091 RGD 
negative regulation of protein kinase activity  IMP 2302091GSK-3 activity as a Tau protein kinaseRGD 
neuron projection morphogenesis  IMP 2302091NGF-induced neurite outgrowth in PC12 cellsRGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
integrin mediated signaling pathway   ISOIlk (Rattus norvegicus)2302091; 2302091 RGD 
integrin mediated signaling pathway   IMP 2302091 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Ilk  (integrin-linked kinase)

Genes (Mus musculus)
Ilk  (integrin linked kinase)

Genes (Homo sapiens)
ILK  (integrin linked kinase)


Additional Information