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Differential inhibition of cytosolic and membrane‐derived protein kinase C activity by staurosporine and other kinase inhibitors
Author(s) -
Budworth Joanna,
Gescher Andreas
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)00227-z
Subject(s) - staurosporine , protein kinase c , cytosol , calphostin c , biochemistry , calphostin , kinase , biology , chemistry , enzyme
The hypothesis was tested that 9 kinase inhibitors with diverse specificities for protein kinase C (PKC), including staurosporine and four of its analogues, interfere differently with PKC derived from either the cytosolic or particulate fractions of MCF‐7 breast carcinoma cells. GF 109203X inhibited the enzyme identically in either preparation. CGP 41251 and calphostin C inhibited cytosolic PKC more effectively than membrane‐derived PKC with ratios of IC 50 (cytosolic PKC) over IC 50 (membrane‐derived PKC) of 0.07 and 0.04, respectively. The other six agents inhibited membrane‐derived PKC more potently than cytosolic enzyme. Staurosporine and RO 31 8220 exhibited IC 50 ratios of 12.3 and 21.6, respectively. The results suggest that there are dramatic differences between kinase inhibitors in their divergent effects on cytosolic and membrane‐derived PKC which should be borne in mind in the interpretation of their pharmacological properties.