Description
1-
NM-
PP1 is a cell permeable inhibitor of kinases that have been mutated, by a single base substitution, to become ‘analog sensitive’ (as), as compared to the wild-
type kinase. 1-
NM-
PP1 was first developed to optimally inhibit v-
Src-
as1, with an I338G substitution, preferentially over v-
Src (IC
50 = 4.2 nM
versus 28 μM, respectively). The homologous mutation in other kinases generated similar analog sensitivity (
e.g., IC
50 = 3.2 nM for c-
Fyn-
as1
versus 1.0 μM for c-
Fyn; 5.0 nM for Cdk2-
as1
versus 29 μM for Cdk2; 8.0 nM for CAMKII-
as1
versus 24 μM for CAMKII). This approach has been used to elucidate functions of several kinases in both mammalian and yeast systems.
References
[1] bishop ac1, ubersax ja, petsch dt, matheos dp, gray ns, blethrow j, shimizu e, tsien jz, schultz pg, rose md, wood jl, morgan do, shokat km. a chemical switch for inhibitor-sensitive alleles of any protein kinase. nature. 2000 sep 21; 407 (6802): 395-401.