Our objective is to determine the mechanism(s) by which prolactin (PRL) stimulates lactational processes and cell proliferation in PRL-target cells. We as well as others have shown that: a) PRL alters the fluidity of plasma membranes, b) TPA and diglycerides (protein kinase C activators) and exogenous phospholipase C will duplicate certain of the differentiative and proliferative effects of PRL in mammary and Nb2 cells, c) the phosphatidyl inositol cycle is stimulated 1-3 hours after adding PRL to mammary and d) PRL stimulates a redistribution of protein kinase C in mammary and Nb2 cells. Studies of the mechanism of action of PRL are important because: a) they will help us understand how PRL regulates lactogenic processes, b) they can help us understand how PRL regulates proliferative processes in normal neoplastic cells, and c) our investigations can serve as a model for understanding how certain hormones in general regulate differentiative and proliferative processes in cells.
Our specific aims are as follows: a) to isolate and characterize phosphorylated proteins that may be involved in the PRL regulation of lactogenic and mitogenic response, b) to determine if the ether phospholipids may be involved in the mechanism of action of PRL on lactogenic and mitogenic responses, c) to determine if the G-protein(s) may be involved in the PRL effects in mammary tissues, d) to determine if PRL has effects on protein kinase C activity in isolated nucleii derived from mouse mammary glands, e) to characterize and define the mechanism by which PRL stimulates lactose biosynthesis in cultured mouse mammary tissues, and f) to determine if and how PRL stimulates case in kinase activity in cultured mammary tissues.
| Campbell, G S; Argetsinger, L S; Ihle, J N et al. (1994) Activation of JAK2 tyrosine kinase by prolactin receptors in Nb2 cells and mouse mammary gland explants. Proc Natl Acad Sci U S A 91:5232-6 |
