Accession Number : ADA306529

Title :   Actions of Tamoxifen and Estrogen on Osteoblast Protein Kinase C Expression.

Descriptive Note : Annual rept. 27 Jun 94-26 Jun 95,

Corporate Author : NORTHWESTERN UNIV EVANSTON IL

Personal Author(s) : Sanders, Jennifer L.

PDF Url : ADA306529

Report Date : JUL 1995

Pagination or Media Count : 30

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).

Descriptors :   *MAMMARY GLANDS, *OSTEOGENESIS, *ESTROGENS, *BREAST CANCER, REQUIREMENTS, CALCIUM, ACTIVATION, STRUCTURAL PROPERTIES, PROTEINS, SUBSTRATES, ZINC, DRUGS, ESTERS, ISOZYMES, FINGERS.

Subject Categories : Medicine and Medical Research
      Anatomy and Physiology

Distribution Statement : APPROVED FOR PUBLIC RELEASE