Abstract

The mechanisms by which proteins are packaged into secretory granules are not understood. Two models that have been proposed are l) self-association or aggregation and 2) recognition of a sorting sequence. These models have not been distinguished experimentally. In GH cells transfected with DNA sequences for human growth hormone, estradiol increases storage of rat prolactin but does not affect storage of human growth hormone. In GH cells transfected with DNA sequences for human prolactin, estradiol does not induce the storage of either rat or human prolactin, although both are still synthesized and secreted. These three molecules are structurally similar. This project will substitute portions of these hormones into each other to determine which amino acids are necessary to allow regulation of storage, and test specific models for packing prolactin into secretory granules.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK046807-03
Application #
2146055
Study Section
Endocrinology Study Section (END)
Project Start
1993-07-15
Project End
1997-06-30
Budget Start
1995-08-10
Budget End
1996-06-30
Support Year
3
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
Yale University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520

  Publications

Keeler, Camille; Hodsdon, Michael E; Dannies, Priscilla S (2004) Is there structural specificity in the reversible protein aggregates that are stored in secretory granules? J Mol Neurosci 22:43-9
Keeler, Camille; Dannies, Priscilla S; Hodsdon, Michael E (2003) The tertiary structure and backbone dynamics of human prolactin. J Mol Biol 328:1105-21
Sankoorikal, Binu-John; Zhu, Yong Lian; Hodsdon, Michael E et al. (2002) Aggregation of human wild-type and H27A-prolactin in cells and in solution: roles of Zn(2+), Cu(2+), and pH. Endocrinology 143:1302-9
Dannies, P S (2001) Concentrating hormones into secretory granules: layers of control. Mol Cell Endocrinol 177:87-93
Lee, M S; Zhu, Y L; Chang, J E et al. (2001) Acquisition of Lubrol insolubility, a common step for growth hormone and prolactin in the secretory pathway of neuroendocrine cells. J Biol Chem 276:715-21
Lee, M S; Wajnrajch, M P; Kim, S S et al. (2000) Autosomal dominant growth hormone (GH) deficiency type II: the Del32-71-GH deletion mutant suppresses secretion of wild-type GH. Endocrinology 141:883-90
Dannies, P S (2000) Protein folding and deficiencies caused by dominant-negative mutants of hormones. Vitam Horm 58:26-Jan
Lee, M S; Dirkx Jr, R; Solimena, M et al. (1998) Stabilization of the receptor protein tyrosine phosphatase-like protein ICA512 in GH4C1 cells upon treatment with estradiol, insulin, and epidermal growth factor. Endocrinology 139:2727-33
Sun, Z; Lee, M S; Rhee, H K et al. (1997) Inefficient secretion of human H27A-prolactin, a mutant that does not bind Zn2+. Mol Endocrinol 11:1544-51
Sun, Z; Li, P S; Dannies, P S et al. (1996) Properties of human prolactin (PRL) and H27A-PRL, a mutant that does not bind Zn++. Mol Endocrinol 10:265-71

Showing the most recent 10 out of 12 publications