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Cyclin-dependent kinase 5 (Cdk5) is required for proper development of the mammalian central nervous system. To be activated, Cdk5 has to associate with its regulatory subunit, p35. We have found that p25, a truncated form of p35, accumulates in neurons in the brains of patients with Alzheimer's disease. This accumulation correlates with an increase in Cdk5(More)
Cyclin-dependent kinase 5 (Cdk5) is a small serine/threonine kinase that plays a pivotal role during development of the CNS. Cables, a novel protein, interacts with Cdk5 in brain lysates. Cables also binds to and is a substrate of the c-Abl tyrosine kinase. Active c-Abl kinase leads to Cdk5 tyrosine phosphorylation, and this phosphorylation is enhanced by(More)
Cyclin-dependent kinase 5 (Cdk5) and its neuron-specific regulator p35 are essential for neuronal migration and for the laminar configuration of the cerebral cortex. In addition, p35/Cdk5 kinase concentrates at the leading edges of axonal growth cones and regulates neurite outgrowth in cortical neurons in culture. The Rho family of small GTPases is(More)
Collapsin response mediator proteins (CRMPs) are a family of neuron-enriched proteins that regulate neurite outgrowth and growth cone dynamics. Here, we show that Cdk5 phosphorylates CRMP1, CRMP2, and CRMP4, priming for subsequent phosphorylation by GSK3 in vitro. In contrast, DYRK2 phosphorylates and primes CRMP4 only. The Cdk5 and DYRK2 inhibitor(More)
BACKGROUND The p35-Cdk5 kinase has been implicated in a variety of functions in the central nervous system (CNS), including axon outgrowth, axon guidance, fasciculation, and neuronal migration during cortical development. In p35(-/-) mice, embryonic cortical neurons are unable to migrate past their predecessors, leading to an inversion of cortical layers in(More)
Neurones are highly specialised cells that can extend over great distances, enabling the complex networking of the nervous system. We are beginning to understand in detail the molecular mechanisms that control the shape of neurones during development. One family of proteins that are clearly essential are the Rho GTPases which have a pivotal role in(More)
The normal formation and function of the mammalian cerebral cortex depend on the positioning of its neurones, which occurs in a highly organized, layer-specific manner. The correct morphology and movement of neurones rely on synchronized regulation of their actin filaments and microtubules. The p21-activated kinase (Pak1), a key cytoskeletal regulator,(More)
Cyclin-dependent kinase 5 is activated by small subunits, of which p35 is the most abundant. The functions of cyclin-dependent kinase 5 signalling in cognition and cognitive disorders remains unclear. Here, we show that in schizophrenia, a disorder associated with impaired cognition, p35 expression is reduced in relevant brain regions. Additionally, the(More)
Epidermal growth factor receptor (EGFR) overexpression has been associated frequently with squamous cell carcinomas (SCC) and SCC cell lines. In most cases the level of EGFR on the tumours from which the cell lines were derived has not been determined, nor have EGFR levels been determined for xenograft tumours from the cell lines. In this study we(More)
PURPOSE Reactivation of neurodevelopmental processes may contribute to neurodegeneration. For example, the proteins cyclin dependent kinase 5 (cdk5) and glycogen synthase kinase 3 beta (GSK3beta), which are essential to normal cortical development, can hyperphosphorylate tau and might contribute to the pathogenesis of Alzheimer's disease. Focal cortical(More)