Previous studies have established that phorbol ester tumor promoters bind to and activate, protein kinase C (PK-C), suggesting a role for PK-C in transformation and tumor promotion. Current studies have been devoted to determining if PK-C activity is altered and regulated in cultured cells in response to growth factors and other hormones, as well as intransformed cells. In pinealocytes, there is a synergistic mechanism operative between aplha1- and beta-adrenergic agonists to elevate cyclic AMP levels. Treatment of pinealocytes with PMA, and with the synthetic diacylglycerol 1-oleoyl, 2-acetyl glycerol (OAG) (both of which act through stimulation of PK-C) was noted to mimic the effects of alpha-adrenergic agonists to enhance beta-adrenergic stimulation of pinealocyte cAMP accumulation. Further, treatment of these cells with the alpha1-aadrenergic agonist, phenylephrine, caused a rapid redistribution of PK-C activity from cytosol to pinealocyte membranes, indicating activation of this enzyme. These results suggest regulatory interaction between PK-C and neurotransmitter-dependent stimulation of cAMP levels. Exposure of an established lymphocyte cell line (CT6) to interleukin-2 (IL-2) was found to cause a rapid and transisent redistribution of PK-C activity from soluble to particulate fraction. Phorbol myristate acetate (PMA) treatment of CT6 cells induced a similar transposition of PK-C in an analogous manner with the exception that PMA-mediate PK-C transposition to the plasma membrane is not readily reversed. Other studies demonstrated that interleukin-3 treatment of FDC-P1 cells provoked a similar decrease in cytosolic PK-C activity concomitant with an increase in membrane-associated PK-C activity. Thus, changes in the activation and subcellular distribution of PK-C in response to growth factors, tumor promoters, and transformation factors, may play a critical role in regulating such cellular processes as cell growth, differentiation, and malignant transformation.

Agency
National Institute of Health (NIH)
Institute
Division of Cancer Biology And Diagnosis (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CB009015-02
Application #
4691888
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Cancer Biology and Diagnosis
Department
Type
DUNS #
City
State
Country
United States
Zip Code