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CDK5

cyclin-dependent kinase 5

Proline-directed serine/threonine-protein kinase essential for neuronal cell cycle arrest and differentiation and may be involved in apoptotic cell death in neuronal diseases by triggering abortive cell cycle re-entry. Interacts with D1 and D3-type G1 cyclins. Phosphorylates SRC, NOS3, VIM/vimentin, p35/CDK5R1, MEF2A, SIPA1L1, SH3GLB1, PXN, PAK1, MCAM/MUC18, SEPT5, SYN1, DNM1, AMPH, SYNJ1, CDK16, RAC1, RHOA, CDC42, TONEBP/NFAT5, MAPT/TAU, MAP1B, histone H1, p53/TP53, HDAC1, APEX1, PTK2/FAK1, huntingtin/HTT, ATM, MAP2, NEFH and NEFM. Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission, by phosphorylating key proteins. Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39), especially in post-mitotic neurons, and promotes CDK5R1 (p35) expression in an autostimulation loop. Phosphorylates many downstream substrates such as Rho and Ras family small GTPases (e.g. PAK1, RAC1, RHOA, CDC42) or microtubule-binding proteins (e.g. MAPT/TAU, MAP2, MAP1B), and modulates actin dynamics to regulate neurite growth and/or spine morphogenesis. Phosphorylates also exocytosis associated proteins such as MCAM/MUC18, SEPT5, SYN1, and CDK16/PCTAIRE1 as well as endocytosis associated proteins such as DNM1, AMPH and SYNJ1 at synaptic terminals. In the mature central nervous system (CNS), regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity; synaptic vesicle exocytosis, vesicles fusion with the presynaptic membrane, and endocytosis. Promotes cell survival by activating anti-apoptotic proteins BCL2 and STAT3, and negatively regulating of JNK3/MAPK10 activity. Phosphorylation of p53/TP53 in response to genotoxic and oxidative stresses enhances its stabilization by preventing ubiquitin ligase-mediated proteasomal degradation, and induces transactivation of p53/TP53 target genes, thus regulating apoptosis. Phosphorylation of p35/CDK5R1 enhances its stabilization by preventing calpain-mediated proteolysis producing p25/CDK5R1 and avoiding ubiquitin ligase-mediated proteasomal degradation. During aberrant cell-cycle activity and DNA damage, p25/CDK5 activity elicits cell-cycle activity and double-strand DNA breaks that precedes neuronal death by deregulating HDAC1. DNA damage triggered phosphorylation of huntingtin/HTT in nuclei of neurons protects neurons against polyglutamine expansion as well as DNA damage mediated toxicity. Phosphorylation of PXN reduces its interaction with PTK2/FAK1 in matrix-cell focal adhesions (MCFA) during oligodendrocytes (OLs) differentiation. Negative regulator of Wnt/beta-catenin signaling pathway. Activator of the GAIT (IFN-gamma-activated inhibitor of translation) pathway, which suppresses expression of a post-transcriptional regulon of proinflammatory genes in myeloid cells; phosphorylates the linker domain of glutamyl-prolyl tRNA synthetase (EPRS) in a IFN-gamma-dependent manner, the initial event in assembly of the GAIT complex. Phosphorylation of SH3GLB1 is required for autophagy induction in starved neurons. Phosphorylation of TONEBP/NFAT5 in response to osmotic stress mediates its rapid nuclear localization. MEF2 is inactivated by phosphorylation in nucleus in response to neurotoxin, thus leading to neuronal apoptosis. APEX1 AP-endodeoxyribonuclease is repressed by phosphorylation, resulting in accumulation of DNA damage and contributing to neuronal death. NOS3 phosphorylation down regulates NOS3-derived nitrite (NO) levels. SRC phosphorylation mediates its ubiquitin-dependent degradation and thus leads to cytoskeletal reorganization. May regulate endothelial cell migration and angiogenesis via the modulation of lamellipodia formation. Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. The complex p35/CDK5 participates in the regulation of the circadian clock by modulating the function of CLOCK protein: phosphorylates CLOCK at 'Thr-451' and 'Thr-461' and regulates the transcriptional activity of the CLOCK-ARNTL/BMAL1 heterodimer in association with altered stability and subcellular distribution.

Gene Name: cyclin-dependent kinase 5
Family/Subfamily: Protein Kinase , CDC2/CDK
Synonyms: CDK5, CDKN5, Cell division protein kinase 5, Crk6, Cyclin-dependent kinase 5, Protein kinase CDK5 splicing, PSSALRE, TPKII catalytic subunit
Target Sequences: NM_004935 NP_004926.1 Q00535

Publications (2)

1
CDK5 positively regulates Notch1 signaling in pancreatic cancer cells by phosphorylation. Qiaoyun Chu, Liyong Wang, Jie Zhang, Wei Wang, Youxin Wang. Cancer medicine. 2021 Jun;;10:3689-3699. [Full Text Article] [PubMed:33960694] [PMC:PMC8178504] Related Antibodies: LS-B353.
2
Idebenone Decreases Aß Pathology by Modulating RAGE/Caspase-3 Signaling and the Aß Degradation Enzyme NEP in a Mouse Model of AD. Hyun-Ju Lee, Ha-Ram Jeong, Jin-Hee Park, Hyang-Sook Hoe. Biology. 2021 Sep;10:938. [Full Text Article] [PubMed:34571815] [PMC:PMC8471964] Related Antibodies: LS-C354604.

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Proteins (13)
Over-Expression Lysate (4)
Recombinant (9)
CDK5 (13)
No (13)
6His, N-terminus (1)
GST (2)
GST, N-terminus (2)
His (1)
His-S (1)
His-SUMO (1)
Myc-DDK (Flag) (5)
Human (11)
293T Cells (2)
E. coli (4)
HEK 293 Cells (3)
Insect Cells (1)
Wheat Germ Extract (3)
Purified (5)
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CDK5 Protein - Purified recombinant protein CDK5 was analyzed by SDS-PAGE gel and Coomassie Blue Staining
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HEK 293 Cells
Myc-DDK (Flag)
33.1 kDa
20 µg/$1,107
CDK5 Protein - 12.5% SDS-PAGE Stained with Coomassie Blue.
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Wheat Germ Extract
GST, N-terminus
10 µg/$479; 25 µg/$670
CDK5 Protein
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E. coli
His-SUMO
49.28 kD
1 mg/$1,355; 100 µg/$420; 20 µg/$323
CDK5 Protein - SDS-PAGE under reducing conditions and visualized by Coomassie blue staining
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E. coli
6His, N-terminus
33 kDa
10 µg/$265; 50 µg/$315; 100 µg/$365; 250 µg/$518
CDK5 Protein - 12.5% SDS-PAGE of human CDK5 stained with Coomassie Blue
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Wheat Germ Extract
GST
57.75 kDa
10 µg/$479; 25 µg/$670
CDK5 Protein - 12.5% SDS-PAGE of human CDK5 stained with Coomassie Blue
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Wheat Germ Extract
GST
57.75 kDa
10 µg/$479; 25 µg/$670
CDK5 Protein - Western validation with an anti-DDK antibody * L: Control HEK293 lysate R: Over-expression lysate
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HEK 293 Cells
Myc-DDK (Flag)
33.1 kDa
100 µg/$494
CDK5 Protein - Western validation with an anti-DDK antibody * L: Control HEK293 lysate R: Over-expression lysate
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HEK 293 Cells
Myc-DDK (Flag)
29.4 kDa
100 µg/$494
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Insect Cells
GST, N-terminus
Less than 1.0 EU/µg protein (determined by LAL method).
59.6 kDa
50 µg/$443
CDK5 Protein
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E. coli
His
100 µg/$361; 500 µg/$739; 20 µg/$261
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E. coli
His-S
26.1 kDa
10 µg/$267; 50 µg/$352; 100 µg/$562; 200 µg/$702; 1 mg/$1,723; 500 µg/$1,298; 5 mg/$2,673; 2 mg/$1,900
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293T Cells
Myc-DDK (Flag)
33.1 kDa
20 µg/$150
CDK5 Protein - Western validation with an anti-DDK antibody * L: Control HEK293 lysate R: Over-expression lysate
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293T Cells
Myc-DDK (Flag)
29.4 kDa
20 µg/$150
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The data on this page has been compiled from LifeSpan internal sources, the National Center for Biotechnology Information (NCBI), and The Universal Protein Resource (UniProt).