Cyclin-dependent kinase 5
Encyclopedia
Cell division protein kinase 5 is an enzyme
that in humans is encoded by the CDK5 gene
. The protein encoded by this gene is part of the cyclin-dependent kinase
family.
CDK5 is required for proper development of the brain and to be activated, CDK5 must associate with CDK5R1
or CDK5R2
. Unlike other cyclin dependent kinases, CDK5 does not also require phosphorylation on the T loop so that binding with the activator is sufficient to activate the kinase.
Cdk5 is involved in the processes of neuronal maturation and migration, phosphorylating the key intracellular adaptor
of the reelin
signaling chain.
Experiments performed on mice lacking p35, a necessary activator of cdk5 in early brain development, showed that the normal layering of neurons was reversed in the cortex. This disrupted lamination again implicated cdk5 in neuronal migration and plasticity.
Cdk5 is also involved in the regulation of synaptic vesicle exocytosis via phosphorylation of munc-18
.
.
It is involved in invasive cancers, apparently by reducing the activity of the actin regulatory protein caldesmon
.
with LMTK2
, NDEL1
, CDK5R1
, Nestin
and PAK1
.
Pareek TK, Keller J, Kesavapany S, Pant HC, Iadarola MJ, Brady RO, Kulkarni AB (2006) Cyclin-dependent kinase 5 activity regulates pain signaling Proc Natl Acad Sci U S A. 2006 Jan 17;103(3):791-6.
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that in humans is encoded by the CDK5 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. The protein encoded by this gene is part of the cyclin-dependent kinase
Cyclin-dependent kinase
thumb|350px|Schematic of the cell cycle. outer ring: I=[[Interphase]], M=[[Mitosis]]; inner ring: M=Mitosis; G1=[[G1 phase|Gap phase 1]]; S=[[S phase|Synthesis]]; G2=[[G2 phase|Gap phase 2]]...
family.
Physiological Role
Recently Cdk5 has emerged as an essential kinase in sensory pathways. Recent reports of Pareek et al. from NIH suggest its necessity in pain signaling.CDK5 is required for proper development of the brain and to be activated, CDK5 must associate with CDK5R1
CDK5R1
Cyclin-dependent kinase 5 activator 1 is an enzyme that in humans is encoded by the CDK5R1 gene.-Interactions:CDK5R1 has been shown to interact with CDK5RAP2, Beta-catenin, Cyclin-dependent kinase 5, Amphiphysin, Protein SET, CAMK2A, Actinin, alpha 1 and PCTK1.-Further reading:...
or CDK5R2
CDK5R2
Cyclin-dependent kinase 5 activator 2 is an enzyme that in humans is encoded by the CDK5R2 gene.-Interactions:CDK5R2 has been shown to interact with Actinin, alpha 1.-Further reading:...
. Unlike other cyclin dependent kinases, CDK5 does not also require phosphorylation on the T loop so that binding with the activator is sufficient to activate the kinase.
Cdk5 is involved in the processes of neuronal maturation and migration, phosphorylating the key intracellular adaptor
DAB1
The Disabled-1 gene encodes a key regulator of Reelin signaling. Reelin is a large glycoprotein secreted by neurons of the developing brain, particularly Cajal-Retzius cells. DAB1 functions downstream of Reln in a signaling pathway...
of the reelin
Reelin
Reelin is a large secreted extracellular matrix protein that helps regulate processes of neuronal migration and positioning in the developing brain by controlling cell–cell interactions. Besides this important role in early development, reelin continues to work in the adult brain. It modulates the...
signaling chain.
Experiments performed on mice lacking p35, a necessary activator of cdk5 in early brain development, showed that the normal layering of neurons was reversed in the cortex. This disrupted lamination again implicated cdk5 in neuronal migration and plasticity.
Cdk5 is also involved in the regulation of synaptic vesicle exocytosis via phosphorylation of munc-18
Munc-18
Munc-18 protein is the mammalian homologue of the unc-18 protein and is a member of the Sec1/Munc18-like protein family...
.
Role in Disease
Dysregulation of this enzyme has been implicated in several neurodegenerative diseases including Alzheimer'sAlzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
.
It is involved in invasive cancers, apparently by reducing the activity of the actin regulatory protein caldesmon
Caldesmon
Caldesmon is a protein that in humans is encoded by the CALD1 gene.Caldesmon is a calmodulin binding protein. Like calponin, caldesmon tonically inhibits the ATPase activity of myosin in smooth muscle....
.
History
CDK5 was originally named NCLK for Neuronal CDC2-Like Kinase due to its similar phosphorylation motif. CDK5 in combination with an activator was also referred to as Tau Protein Kinase II.Interactive pathway map
Interactions
Cyclin-dependent kinase 5 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with LMTK2
LMTK2
Serine/threonine-protein kinase LMTK2 also known as Lemur tyrosine kinase 2 is an enzyme that in humans is encoded by the LMTK2 gene.- Function :...
, NDEL1
NDEL1
Nuclear distribution protein nudE-like 1 is a protein that in humans is encoded by the NDEL1 gene.This gene encodes a thiol-activated oligopeptidase that is phosphorylated in M phase of the cell cycle...
, CDK5R1
CDK5R1
Cyclin-dependent kinase 5 activator 1 is an enzyme that in humans is encoded by the CDK5R1 gene.-Interactions:CDK5R1 has been shown to interact with CDK5RAP2, Beta-catenin, Cyclin-dependent kinase 5, Amphiphysin, Protein SET, CAMK2A, Actinin, alpha 1 and PCTK1.-Further reading:...
, Nestin
Nestin (protein)
Nestin is a type VI intermediate filament protein. These intermediate filament proteins are expressed mostly in nerve cells where they are implicated in the radial growth of the axon...
and PAK1
PAK1
Serine/threonine-protein kinase PAK 1 is an enzyme that in humans is encoded by the PAK1 gene.-Interactions:PAK1 has been shown to interact with C-Raf, NCK1, LIMK1, RAC1, ARHGEF2, BMX, ARPC1B, DYNLL1, Cyclin-dependent kinase 5, PAK1IP1 and CDC42....
.
Further reading
Pareek TK, Keller J, Kesavapany S, Agarwal N, Kuner R, Pant HC, Iadarola MJ, Brady RO, Kulkarni AB (2007) Cyclin-dependent kinase 5 modulates nociceptive signaling through direct phosphorylation of transient receptor potential vanilloid 1 1: Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):660-5.Pareek TK, Keller J, Kesavapany S, Pant HC, Iadarola MJ, Brady RO, Kulkarni AB (2006) Cyclin-dependent kinase 5 activity regulates pain signaling Proc Natl Acad Sci U S A. 2006 Jan 17;103(3):791-6.