Cyclin D2 Interacts with cdk‐5 and Modulates Cellular cdk‐5/p35 Activity

Guidato, Sonia; McLoughlin, Declan M.; Grierson, Andrew J.; Miller, Christopher C.J.

doi:10.1046/j.1471-4159.1998.70010335.x

Cited by 39 publications

(28 citation statements)

References 39 publications

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“…However, Guidato et al reported that cyclin D2 modulates the activity of the Cdk5-p35 complex, although the specific mechanism was not investigated in this study (Guidato et al, 1998). In agreement, a recent study revealed that cyclin D1 modulates Cdk5-p35 activity, possibly by competing with p35 binding to Cdk5 (Modi et al, 2012).…”

Section: Cyclin Dsupporting

confidence: 81%

Cdk5 activity in the brain – multiple paths of regulation

Shah

Lahiri

2014

Journal of Cell Science

167

133

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Cyclin dependent kinase-5 (Cdk5), a family member of the cyclindependent kinases, plays a pivotal role in the central nervous system. During embryogenesis, Cdk5 is indispensable for brain development and, in the adult brain, it is essential for numerous neuronal processes, including higher cognitive functions such as learning and memory formation. However, Cdk5 activity becomes deregulated in several neurological disorders, such as Alzheimer's disease, Parkinson's disease and Huntington's disease, which leads to neurotoxicity. Therefore, precise control over Cdk5 activity is essential for its physiological functions. This Commentary covers the various mechanisms of Cdk5 regulation, including several recently identified protein activators and inhibitors of Cdk5 that control its activity in normal and diseased brains. We also discuss the autoregulatory activity of Cdk5 and its regulation at the transcriptional, post-transcriptional and post-translational levels. We finally highlight physiological and pathological roles of Cdk5 in the brain. Specific modulation of these protein regulators is expected to provide alternative strategies for the development of effective therapeutic interventions that are triggered by deregulation of Cdk5.

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Section: Cyclin Dsupporting

confidence: 81%

Cdk5 activity in the brain – multiple paths of regulation

Shah

Lahiri

2014

Journal of Cell Science

167

133

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“…PAK1 activities in transfected CHO cells were assayed essentially as described previously by us for other kinases (21,22). Briefly, cells were co-transfected with PAK1, Rac, and ALS2, ALS2⌬DH, or vector encoding CAT as a negative control.…”

Section: Methodsmentioning

confidence: 99%

ALS2/Alsin Regulates Rac-PAK Signaling and Neurite Outgrowth

Tudor

Perkinton

Schmidt

et al. 2005

Journal of Biological Chemistry

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Rac and its downstream effectors p21-activated kinase (PAK) family kinases regulate actin dynamics within growth cones to control neurite outgrowth during development. The activity of Rac is stimulated by guanine nucleotide exchange factors (GEFs) that promote GDP release and GTP binding. ALS2/Alsin is a recently described GEF that contains a central domain that is predicted to regulate the activities of Rac and/or Rho and Cdc42 activities. Mutations in ALS2 cause some recessive familial forms of amyotrophic lateral sclerosis (ALS) but the function of ALS2 is poorly understood. Here we demonstrate that ALS2 is present within growth cones of neurons, in which it co-localizes with Rac. Furthermore, ALS2 stimulates Rac but not Rho or Cdc42 activities, and this induces a corresponding increase in PAK1 activity. Finally, we demonstrate that ALS2 promotes neurite outgrowth. Defects in these functions may therefore contribute to motor neuron demise in ALS.

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“…Other activators of Cdk5 include 2 neuronspeci c proteins, the P39 protein (Tang et al, 1995), and the vesicle trafficking-associated protein, Munc-18 (Shetty et al, 1995). Interestingly, cyclin-D and cyclin-E molecules, which regulate Cdk activity in proliferating cells, bind but do not activate Cdk5 (Guidato et al, 1998;Miyajima et al, 1995;Xiong et al, 1992).…”

Section: Dk5mentioning

confidence: 99%

Expression and localization of cyclin-dependent kinase 5 in apoptotic human glioma cells

Catania¹

2001

Neuro-Oncology

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Neuro-Oncology nA P R I L 2 0 0 1 89 Cyclin-dependent kinase 5 (Cdk5), a member of the cyclin-dependent kinase family, is expressed predominately in mature neurons and is implicated in neurite extension, neuronal migration, and neuronal differentiation. Cdk5 protein expression also has been associated with apoptosis in a number of nonneuronal model systems. In normal brain, substrates for Cdk5 include neuro lament and tau proteins. Because human tumors of glial origin can express neuronal proteins, we examined whether Cdk5 and its activator protein, P35, are present in early passage human glioblastoma multiforme (GBM) cells lines and primary tumor specimens. Here we report the expression of Cdk5 and an "active" proteolytic form of P35 in human GBM cells and demonstrate kinase activity of the holoenzyme. We also show that Cdk5 kinase activity and expression of its activator protein, P35, is increased in the human GBM cell line M059J after exposure to ionizing radiation and that P35 is localized within M059J cells undergoing apoptosis. These results suggest a possible role for Cdk5 in mediating apoptosis in human GBM cells. Neuro-Oncology 3, 89-98, 2001 (Posted to Neuro-Oncology [serial online], Doc. 00-038, February 15, 2001

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Cyclin D2 Interacts with cdk‐5 and Modulates Cellular cdk‐5/p35 Activity

Cited by 39 publications

References 39 publications

Cdk5 activity in the brain – multiple paths of regulation

Cdk5 activity in the brain – multiple paths of regulation

ALS2/Alsin Regulates Rac-PAK Signaling and Neurite Outgrowth

Expression and localization of cyclin-dependent kinase 5 in apoptotic human glioma cells

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