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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1996-10-23
pubmed:abstractText
Cyclin-dependent kinase 5(cdk5) is highly homologous to other members of the cdk family that are known to function in proliferating cells. Despite the structural similarity, cdk5-associated histone H1 kinase activity is only detectable in postmitotic neurons of the central nervous system (CNS). p35 is a neuronal-specific cdk5 regulator that activates cdk5 kinase activity upon association. The cdk5/p35 kinase activity increases during the progression of CNS neurogenesis, suggesting a function of cdk5 in neuronal differentiation. Here we show that both cdk5 and p35 proteins are present in the growth cones of developing neurons. The staining pattern of cdk5 in the growth cones is similar to that of actin filaments but not microtubules. To address the functional significance of the cdk5/p35 kinase in neurogenesis, we ectopically expressed wild-type or mutant kinases in cortical cultures. Expression of dominant-negative mutants of cdk5 (cdk5N144 and cdk5T33) inhibited neurite outgrowth, which was rescued by coexpression of the wild-type proteins. A similar extent of neurite outgrowth inhibition was obtained by transfection of an antisense p35 construct, which in turn was only rescued by p35 but not cdk5 coexpression. In contrast, longer neurites were elaborated in neurons that coexpressed exogenous cdk5 and p35. These observations suggest that the cdk5/p35 kinase plays a critical role in neurite outgrowth during neuronal differentiation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0890-9369
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
816-25
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:8846918-Animals, pubmed-meshheading:8846918-Cell Compartmentation, pubmed-meshheading:8846918-Cell Differentiation, pubmed-meshheading:8846918-Cells, Cultured, pubmed-meshheading:8846918-Cerebral Cortex, pubmed-meshheading:8846918-Cyclin-Dependent Kinase 5, pubmed-meshheading:8846918-Cyclin-Dependent Kinases, pubmed-meshheading:8846918-Fluorescent Antibody Technique, pubmed-meshheading:8846918-Mutagenesis, Site-Directed, pubmed-meshheading:8846918-Nerve Tissue Proteins, pubmed-meshheading:8846918-Neurites, pubmed-meshheading:8846918-Neurons, pubmed-meshheading:8846918-Protein-Serine-Threonine Kinases, pubmed-meshheading:8846918-Rats, pubmed-meshheading:8846918-Rats, Inbred Strains, pubmed-meshheading:8846918-Recombinant Fusion Proteins, pubmed-meshheading:8846918-Transfection
pubmed:year
1996
pubmed:articleTitle
The cdk5/p35 kinase is essential for neurite outgrowth during neuronal differentiation.
pubmed:affiliation
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
pubmed:publicationType
Journal Article