This proposal deals with muscle (M) and brain (B) specific creatine kinases. The B-isozyme is the fetal form and during muscle differentiation there is a switch from the B-specific to the M-specific isozyme. There is also evidence that the B-isozyme is a major protein induced by estrogen in the uterus. The purpose of the proposal is to study the tissue specific expression of creatine kinase genes and the estrogen induction of the B-isozyme. The starting point for the work is the M- and B-isozyme cDNA clones which we have isolated and sequenced. These are being used to isolate rabbit creatine kinase genes. The genes are to be introduced into mammalian cells and manipulated through a series of mutagenic procedures in order to learn about sequences which control tissue specific expression and estrogen induction of the B-isozyme. Two mammalian gene transfer systems are under investigation. Preliminary experiments have detected a potential creatine kinase homologue in yeast. Further experiments will attempt to determine whether authentic creatine (or guanidino) kinase occurs in yeast and, if so, whether it is an essential protein. The system may offer an additional route to explore cellular roles of creatine kinases.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM034366-01A1
Application #
3285238
Study Section
Molecular Biology Study Section (MBY)
Project Start
1985-08-30
Project End
1988-07-31
Budget Start
1985-08-30
Budget End
1986-07-31
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Type
Schools of Arts and Sciences
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
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Ch'ng, J L; Mulligan, R C; Schimmel, P et al. (1989) Antisense RNA complementary to 3' coding and noncoding sequences of creatine kinase is a potent inhibitor of translation in vivo. Proc Natl Acad Sci U S A 86:10006-10
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