Our objective is to determine the mechanism(s) by which prolactin (PRL) stimulates lactational processes and cell proliferatin in PRL-target cells. We and others have shown that: a) PRL alters the fluidity of plasma membranes, b) TPA (a protein kinase C activator) and exogeneously added phospholipase C will duplicate certain of the differentiative and proliferative actions of PRL in its target cells, and c) PRL stimulates [3H] choline release from isolated mammary gland membrane preparations. Studies of the mechanism of PRL action 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 and neoplastic cells, and c) such investigations can serve as a model for understanding how certain hormones in general have effects on differentiative and proliferative processes in target cells.
Our specific aims are: a) to determine if the primary action of PRL on its target cells is the stimulation of a phosphodiesterase enzyme(s) (PLC and/or SPGase) in the plasma membrane that catalyzes the release of choline phosphate from phosphatidyl choline (PC) and/or sphingomyelin (SPG). The possible effect of PRL on the activity of this enzyme(s) will be identified and characterized; in addition, we will determine if the products of the action of this enzyme(s) will duplicate any or all of the actions of PRL on its target cells, b) to carry out further studies on the involvement of protein kinase C in the PRL actions on cells, c) to identify any proteins that are phosphorylated in response to PRL during the early times after administration of PRL to its target cells, and d) to determine the possible important of the incorporation of the polyamines into the ornithine decarboxylase molecule, which may subsequently become a subunit of RNA polymerase I.
| 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 |
