Integrin alpha(1) beta(1)-mediated activation of cyclin-dependent kinase 5 activity is involved in neurite outgrowth and human neurofilament protein H Lys-Ser-Pro tail domain phosphorylation.
Cellular adhesion to the extracellular matrix is mediated by a diverse class of alpha/beta heterodimeric receptors known as integrins, which transduce signals to activate multiple intracellular signal transduction pathways within the cells. The signaling pathway linking integrins to mediate neuronal process outgrowth is not well understood. Here, we have provided evidence that intracellular signaling by the alpha(1)beta(1) integrin-induced activation of cyclin-dependent kinase 5 (cdk5) is involved in neurite outgrowth and human neurofilament protein H (hNF-H) Lys-Ser-Pro (KSP) tail domain phosphorylation in differentiated human SH-SY5Y cells. The integrin alpha(1) and beta(1) monoclonal antibodies and BL-1, a specific cdk5 inhibitor, inhibited these effects. We also demonstrated that cdk5 activity and hNF-H KSP tail domain phosphorylation were increased in cdk5/p35 and hNF-H tail domain co-transfected HEK293 cells grown on laminin. This increased hNF-H tail domain phosphorylation was triggered by cdk5 activation. Taken together, these results indicated that cdk5 may play an important role in promoting neurite outgrowth and hNF-H tail KSP domain phosphorylation through the integrin alpha(1)beta(1) signaling pathway.
Laboratory of Neurochemistry, National Institute of Neurological Diseases and Stroke, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-4130, USA.
B S
BS
Li
L
L
Zhang
J
J
Gu
N D
ND
Amin
H C
HC
Pant
D000906:Antibodies / Q000494:pharmacology; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D039222:Integrin alpha1beta1; D016023:Integrins / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism / Q000494:pharmacology; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism; D016501:Neurites / Q000378:metabolism*; D009447:Neuroblastoma; D016900:Neurofilament Proteins / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000502:physiology
D000906:Antibodies; D001425:Bacterial Outer Membrane Proteins; D039222:Integrin alpha1beta1; D016023:Integrins; D007797:Laminin; D008074:Lipoproteins; D016900:Neurofilament Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; C051774:neurofilament protein H; D014212:Tretinoin; D051360:Cyclin-Dependent Kinase 5; C495905:CDK5 protein, human; D018844:Cyclin-Dependent Kinases