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Structural and functional studies of protein kinase C
G M Housey1, M D Johnson, W L Hsiao
1Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
Advances in Experimental Medicine and Biology
|January 1, 1988
Summary
Protein kinase C (PKC) is crucial for cell growth and acts as a receptor for tumor promoters. Overexpressing PKC in cells causes abnormal growth, demonstrating its role in cancer development.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- Protein kinase C (PKC) is fundamental to cellular growth control in eukaryotes.
- PKC is the high-affinity intracellular receptor for tumor promoters, making it a key focus in cancer research.
- Understanding PKC's role in growth control and tumor promotion is essential.
Purpose of the Study:
- To detail the role of Protein Kinase C (PKC) in cellular growth control and tumor promotion.
- To investigate the functional characteristics of the PKC beta 1 form.
- To generate and analyze cell lines overexpressing PKC beta 1.
Main Methods:
- Isolation of cDNA clones encoding various forms of PKC.
- Determination of the primary structure of PKC beta 1.
- Generation of rat fibroblast cell lines stably overexpressing PKC beta 1 cDNA.
Main Results:
- PKC beta 1 structure includes a cysteine-rich domain for binding and a catalytic domain.
- Overexpressing PKC beta 1 led to a 20- to 53-fold increase in PKC activity and enhanced phorbol ester receptor binding.
- PKC-overexpressing cells showed enhanced morphologic changes, increased growth density, and anchorage-independent growth in soft agar.
Conclusions:
- Overproduction of a single PKC form (beta 1) is sufficient to induce abnormal growth in rat fibroblasts.
- PKC plays a critical role in normal cellular growth control.
- PKC mediates cellular effects of phorbol ester tumor promoters.