K252a is an

alkaloid Alkaloids are a broad class of natural product, naturally occurring organic compounds that contain at least one nitrogen atom. Some synthetic compounds of similar structure may also be termed alkaloids. Alkaloids are produced by a large varie ...

isolated from ''

Nocardiopsis ''Nocardiopsis'' is a bacterial genus from the family Nocardiopsaceae which can produces some antimicrobial compounds, including thiopeptides. ''Nocardiopsis'' occur mostly in saline and alkaline soils. Phylogeny The currently accepted taxonomy ...

bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...

. This

staurosporine Staurosporine (antibiotic AM-2282 or STS) is a natural product originally isolated in 1977 from the bacterium '' Streptomyces staurosporeus''. It was the first of over 50 alkaloids that were discovered to share this type of bis-indole chemical st ...

analog is a highly potent cell permeable

inhibitor Inhibitor or inhibition may refer to: Biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotransmi ...

of CaM

kinase In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...

and phosphorylase kinase (IC₅₀ = 1.8 and 1.7 nmol/ L, respectively). At higher concentrations it is also an efficient inhibitor of serine/threonine protein kinases (IC₅₀ of 10 to 30 nmol/L).Tapley, P. ''et al.'' (1992) Oncogene 7, 371. K252a is reported to promote myogenic differentiation in C2 mouse myoblasts and has been shown to block the neuronal differentiation of rat pheochromocytoma PC12 cells by inhibition of trk tyrosine kinase activity. K252a has been reported in preclinical research as a potential treatment for

psoriasis Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by patches of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small localized patches to complete b ...

. K252a inhibits tyrosine

phosphorylation In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writ ...

of Trk A induced by NGF. PC12 cells were incubated in the presence or absence of 10 ng/ml NGF with or without various concentrations of K252a.

See also

References

Further reading