Cell Signaling Technology

Product Pathways - Neuroscience

p35 Antibody #2673

Applications Reactivity MW (kDa) Source
W IP IF-F M R (H) 25 to 35 Rabbit

Applications Key:  W=Western Blotting  IP=Immunoprecipitation  IF-F=Immunofluorescence (Frozen)
Reactivity Key:  H=Human  M=Mouse  R=Rat
Species enclosed in parentheses are predicted to react based on 100% sequence homology. Species cross-reactivity is determined by Western blot.

Specificity / Sensitivity

p35 Antibody detects endogenous levels of total p35 protein. Calpain proteolyticly cleaves p35 to p25 upon neurotoxic insult and p35 Antibody can detect p25.

Source / Purification

Polyclonal antibodies are produced by immunizing rabbits with a synthetic peptide (KLH-coupled) corresponding to the sequence of human p35/p25. Antibodies are purified by protein A and peptide affinity chromatography.

Western Blotting

Western Blotting

Western blot analysis of extracts from mouse and rat brain, using p35 Antibody.

IF-F

IF-F

Confocal immunofluorescent image of mouse cerebellum labeled with p35 Antibody (red) and CREB (86B10) #9104 (green). Blue pseudocolor = DRAQ5™ (fluorescent DNA dye).

Background

Cyclin-dependent kinases (CDKs) are serine/threonine kinases that are activated by cyclins and govern eukaryotic cell cycle progression. While CDK5 shares high sequence homology with its family members, it is thought mainly to function in postmitotic neurons, regulating the cytoarchitecture of these cells. Analogous to cyclins, p35 and p39 associate with and activate CDK5 despite the lack of sequence homology. CDK5 is ubiquitously expressed, but high levels of kinase activity are detected primarily in the nervous system due to the narrow expression pattern of p35 and p39 in post-mitotic neurons. A large number of CDK5 substrates have been identified although no discrete substrates have been attributed as a function of p35 vs. p39. Amongst many, substrates of CDK5 include p35 and p39. p35 is rapidly degraded (T1/2 <20 min) by the ubiquitin-proteasome pathway (1). However, p35 stability increases as CDK5 kinase activity decreases, and this is likely a result of decreased phosphorylation of p35 at Thr138 by CDK5 (2). NGF activates Erk and EGR1, and induces p35 expression in PC12 cells (3). Proteolytic cleavage of p35 by calpain produces p25 upon neurotoxic insult, resulting in prolonged activation of CDK5 by p25. Accumulation of p25 is found in neurodegenerative diseases such as Alzheimer's disease and Amyotrophic Lateral Sclerosis (ALS) (4-5).

  1. Dhavan, R. and Tsai, L.H. (2001) Nat. Rev. Mol. Cell Biol. 2, 749-759.
  2. Patrick, G.N. et al. (1998) J. Biol. Chem. 273, 24057-24064.
  3. Harada, T. et al. (2001) Nat. Cell Biol. 3, 453-459.
  4. Lee, M.S. et al. (2000) Nature 405, 360-364.
  5. Kusakawa, G. et al. (2000) J. Biol. Chem. 275, 17166-17172.

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