K252a

K252a

Potent Inhibitor of Protein Kinase A, Protein Kinase C and Protein Kinase G.

Product#:

K-150

Sizes:

50 mg

5 x 50 mg

0.47 mg

and has been shown to block the neuronal differentiation of rat pheochromocytoma PC12 cells by inhibition of trk tyrosine kinase activity.¹⁰ Paradoxically K252a exerts neurotrophic effects on primary sensory neurons, neuroblastoma cells, PC12 cells, and central neurons.^11-13

M.W.:

467

CAS No.:

[97161-97-2]

Structure:

.

Purity:

Greater than 99% as evaluated by HPLC.

Bioassay:

The biological activity was tested to confirm the ability of K252a to inhibit the phosphorylation of MARCKS by PKC and TrkA.

K252a inhibits the serine phophorylation of Myristoylated alanin-rich protein kinase C substrate (MARCKS). C6 glioma cells were grown to 70% confluency and then serum starved for 18 h. The cells were preincubated for 30 min in different concentrations of K252a and stimulated with TPA (2mM) for 30 min and the cell extracts were prepared for Western blotting. The protein were probed with anti-Phospho (ser)- MARCKS.

K252a inhibits tyrosine phosphorylation 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. The inhibitory effect of K252a on neurite outgrowth stimulated by  NGF is presented in the picture.

References:

1.	Ruegg, U.T. et al. (1989) Tips 10, 218.
2.	Eliot, L.H. et al. (1990) B.B.R.C. 171, 148.
3.	Simpson, D.l. et al. (1991) J. Neurosci. Res, 28, 148.
4.	Chin, L.S. et al. (1999) Cancer Invest. 17, 391.
5.	Tapley, P. et al. (1992) Oncogene 7, 371.
6.	Hashimoto, S. (1998) J. Cell Biol. 107, 1531.
7.	Kase, H. et al. (1987) B.B.R.C. 142, 436.
8.	Hirayama E. et al. (2001) B.B.R.C. 285, 1237.
9.	Tapley, P. et al. (1992) Oncogene 7, 371.
10.	Borasio, G.D. Neurosci. Lett. (1990) 108, 207.
11.	Hashimoto, S. et al. (1989) Exp. Cell Res. 184, 351.
12.	Tischler, A.S. et al. (1991) J. Biol. Chem. 266, 1141.

Recent Articles Citing Use of this Product:

1. Jeanblanc, J. et al. (2006) J. Neurosci. 26, 1457.

2. Lopez-Dominguez, A.M. et al. (2006) J. Physiol. 574,  349.

3. Acosta, C.G. et al. (2001) J. Neuroscience 21, 8873.

K252a is an alkaloid isolated from Nocardiopisis sp.soil fungi.This ATP analog is a highly potent cell permeable inhibitor of CaM kinase and phosphorylase kinase (IC₅₀= 1.8 and 1.7 nM respectively). At higher concentrations it is also an efficient inhibitor of serine/threonine protein kinases (IC₅₀ of 10 to 30 nM).^1-8

It is reported to promote myogenic differentiation in C2 mouse myoblasts ⁹