The structure of a hormone determines its function in target tissues. Recently, we have identified phosphorylated bovine prolactin (bPRL) and growth hormone (bGH). We have isolated and characterized the phosphorylated bPRL and have preliminary evidence that the structure of phosphorylated bPRL is different from nonphosphorylated bPRL. The hypothesis to be tested in this proposal will determine if in vivo posttranslational phosphorylation of either bPRL or bGH creates a hormone messenger with biological activities different from those of the native hormone. Posttranslational phosphorylation offers a mechanism by which the pituitary can specifically tailor several endocrine messages from a single gene product. These findings may have significant implications in our understanding of the physiology of the endocrine system. The bovine pituitary provides a system where isolation and characterization of PRL and GH are neither complicated by the structural and biological consequences of glycosylation nor limited by tissue availability. The specific objectives to test the hypothesis are: 1.Isolate and structurally characterize phosphorylated bPRL and bGH. 2. Determine the biological actions of phosphorylated bPRL and bGH in a series of bioassays and receptor assays and compare these activities with those induced by nonphosphorylated and reference preparations. If the hypothesis is correct then: 3.Determine the physiological agents that regulate the phosphorylation and secretion of bovine prolactin and growth hormone.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Modified Research Career Development Award (K04)
Project #
5K04DK001989-05
Application #
2133626
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1991-08-01
Project End
1996-07-31
Budget Start
1995-08-01
Budget End
1996-07-31
Support Year
5
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Ohio State University
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210
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Wicks, J R; Brooks, C L (1999) GH kinase activity in bovine anterior pituitary subcellular fractions. Endocrine 10:77-82
Brooks, C L; Saiduddin, S (1998) Phosphorylation of bovine prolactin eliminates luteotropic activity in the rat. Life Sci 63:1281-7
Peterson, F C; Brooks, C L (1997) Identification of a motif associated with the lactogenic actions of human growth hormone. J Biol Chem 272:21444-8
Maciejewski, P M; Peterson, F C; Anderson, P J et al. (1995) Mutation of serine 90 to glutamic acid mimics phosphorylation of bovine prolactin. J Biol Chem 270:27661-5
Wicks, J R; Brooks, C L (1995) Biological activity of phosphorylated and dephosphorylated bovine prolactin. Mol Cell Endocrinol 112:223-9
Brooks, C L; Isaacs, L A; Wicks, J R (1994) Preparative purification of phosphorylated and nonphosphorylated bovine prolactins. Mol Cell Endocrinol 99:301-5
Kim, B G; Brooks, C L (1993) Isolation and characterization of phosphorylated bovine prolactin. Biochem J 296 ( Pt 1):41-7