Actions of Tamoxifen and Estrogen on Osteoblast Protein Kinase C Expression.
Abstract
The protein kinase C (PKC) enzyme family consists of at least 11 isozymes with unique tissue distributions and substrate specificities (1-6). These isozymes comprise at least three classes, termed the conventional, novel, and atypical isozymes; a fourth class has also been proposed, the charter member being PKC-u. The isozymes within a given class share common activation requirements due to structural features within that class. The conventional isozymes, PKC-a, -B(I), Beta(II), and gamma, require phosphatidylserine (PS), diacylglycerol (DAG), and calcium (Ca2+) for activation. The novel isozymes, PKC-sigma, -Epsilon, -n, and -0, also require PS and DAG for activation, but are Ca2+-independent. The atypical isozymes, PKC-, -t/lambda, require PS but are both Ca2+- and DAG-independent. The activation requirements of PKC-u are most like those of the novel isozymes, but several features separate u from this class, including the presence of two unique hydrophobic amino-terminal domains in u (5). The common structural features of a given class of PKCs also confer a similar sensitivity of these isozymes to pharmacological agents such as phorbol esters. Phorbol ester-sensitive PKC isozymes are activated by acute phorbol treatment (7) but down-regulated with more prolonged exposures (8). Phorbol esters act as DAG analogs; therefore, the conventional and novel PKC isozymes, which bind DAG, also bind and are responsive to phorbol esters (2). In contrast, the atypical isozymes, which lack one of the two zinc fingers necessary to bind DAG, also fail to bind phorbol esters and are generally phorbol-insensitive (2,4).
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1995
- Accession Number
- ADA306529
Entities
People
- Jennifer L. Sanders
Organizations
- Northwestern University