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Off the Trk (with K252a)

The four mammalian neurotrophins (NTs) – NGF, BDNF, NT-3, and NT-4 – are renowned regulators of neural plasticity, function and survival. They differentially activate tropomyosin-related kinase (Trk) receptors: TrkA (binds NGF), TrkB (binds BDNF and NT-4), and TrkC (binds NT-3). NT-3 can also activate TrkA and TrkB, albeit less efficiently. The Trk-NT interaction occurs mainly at the receptor’s most proximal immunoglobulin domain and initiates a kinase cascade. The activity of Trks can be modulated by K252a, which inhibits the phosphorylation of the receptors. In this short synopsis we report the use of Alomone Labs K252a in the literature.

Trk Inhibition by K252a

K252a is a potent inhibitor of protein kinase C isolated from Nocardiopsis. It selectively prevents the phosphorylation of Trk receptors (IC50= 3nM)6,10. Alomone Labs K252a (#K-150) interference with TrkB’s activity has been insightful in behavioral studies; it helped validate BDNF’s ability to exert long term potentiation (LTP) – which correlates with learning and memory – at amygdalar synapses, where it attenuates fear consolidation7. In hippocampal mossy-fiber synapses, it prevented BDNF-organized neural morphology4 and high frequency stimulation (HFS)-dependent LTP balance9. Intrastriatal administration of K252a in mice, prevented the maladaptive neuronal plasticity observed in epileptic seizure models – where TrkB is overexpressed3. Also, administration of the Trk inhibitor potentiated cocaine place-preference response in post-weanling mice otherwise defiant to cocaine psychostimulation8 (Figure 1).

PC12 cells could differentiate, migrate and survive when co-cultured with human periodontal ligament (PDL) stem cells11. This effect could be reversed when 200-500 nM of K252a was applied to the medium, thereby suggesting a pivotal role for NTs in realizing these phenomena11-12.

Figure 1. K252a Potentiates Cocaine Place-Preference Response in Post-Weanling Mice.
Postweanling mice were pretreated with K252a (#K-150) or vehicle (i.c.v.) 30 min before being conditioned with cocaine (20 mg/kg) or saline in a 7d conditioning paradigm. On test day 8, preference scores were determined in the absence of drug administration. K252a treatment before cocaine (K252a, i.c.v. plus Coc, i.p.) on conditioning days 1–7 resulted in a significant place preference to the cocaine-paired environment (**p< 0.01). Data are shown as mean ± SEM (n=9 –12).
Adapted from reference 8 with permission of The Society for Neuroscience.

Although the activation of Trks is neuroprotective and rescues apoptosis targeted cells5, this very trait encourages tumorigenic cells to proliferate, as was shown for colorectal cancer and diffuse large B-cell lymphoma cells which entered apoptosis upon treatment with K252a or via activation of p75NTR1-2.

Alomone Labs is pleased to offer K252a (#K-150). We also offer highly specific antibodies to all Trk receptors:Anti-TrkA (extracellular) antibody (#ANT-018), Anti-TrkB (extracellular) antibody (#ANT-019) and Anti-TrkC (extracellular) antibody (#ANT-020). All three antibodies recognize extracellular epitopes, highly advantageous for detecting the receptors in live cell imaging.


  1. Akil, H. et al. (2011) PLoS One 6, e25097.
  2. Bellanger, C. et al. (2011) PLoS One 6, e27213.
  3. Ghiglieri, V. et al. (2010) Neuropsychopharmacology 35, 1531.
  4. Gomez-Palacio-Schjetnan, A. and Escobar, M.L. (2008) Neurosci. Lett. 445, 62.
  5. Heck, N. et al. (2008) Cereb. Cortex 18, 1335.
  6. Knusel, B. and Hefti, F. (1992) J. Neurochem. 59, 1987.
  7. Meis, S. et al. (2012) J. Physiol. 590, 193.
  8. Niculescu, M. et al. (2008) J. Neurosci. 28, 1198.
  9. Schjetnan, A.G. and Escobar, M.L. (2012) Hippocampus 22, 1.
  10. Tapley, P. et al. (1992) Oncogene 7, 371.
  11. Tomokiyo, A. et al. (2012) J. Cell. Physiol. 227, 2040.
  12. Ulmann, L. et al. (2009) Neuroscience 159, 514.