Stimulation of protein kinase C activity in cells expressing human parathyroid hormone receptors by C- and N-terminally truncated fragments of parathyroid hormone 1-34

Citation
Jf. Whitfield et al., Stimulation of protein kinase C activity in cells expressing human parathyroid hormone receptors by C- and N-terminally truncated fragments of parathyroid hormone 1-34, J BONE MIN, 16(3), 2001, pp. 441-447
Citations number
38
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
JOURNAL OF BONE AND MINERAL RESEARCH
ISSN journal
08840431 → ACNP
Volume
16
Issue
3
Year of publication
2001
Pages
441 - 447
Database
ISI
SICI code
0884-0431(200103)16:3<441:SOPKCA>2.0.ZU;2-X
Abstract
The parathyroid hormone (PTH) fragment PTH(1-34) stimulates adenylyl cyclas e, phospholipase C (PLC), and protein kinase C's (PKCs) in cells that expre ss human, opossum, or rodent type 1 PTH/PTH-related protein (PTHrP) recepto rs (PTHR1s). Certain carboxyl (C)-terminally truncated fragments of PTH(1-3 4), such as human PTH(1-31) [hPTH-(1-31)NH2], stimulate adenylyl cyclase bu t not PKCs in rat osteoblasts or PLC and PKCs in mouse kidney cells. The hP TH(1-31)NH2 peptide does fully stimulate PLC in HKRK B7 porcine renal epith elial cells that express 950,000 transfected hPTHR1s per cell. Amino (N)-te rminally truncated fragments, such as bovine PTH(3-34) [bPTH(3-34)1, hPTH(3 -34)NH2, and hPTH(13-34), stimulate PKCs in Chinese hamster ovary (CHO) cel ls expressing transfected rat receptors, opossum kidney cells, and rat oste oblasts, but an intact N terminus is needed to stimulate PLC via human PTHR 1s in HKRK B7 cells. We now report that the N-terminally truncated analogs bPTH(3-34)NH2 and hPTH(13-34)OH do activate PKC via human PTHR1s in HKRK B7 cells, although less effectively than hPTH(1-34)NH2 and hPTH(1-31)NH2. Mor eover, in a homologous human cell system (normal foreskin fibroblasts), the se N-terminally truncated fragments stimulate PKC activity as strongly as h PTH(1-34)NH2 and hPTH(1-31)NH2. Thus, it appears that unlike their opossum and rodent equivalents, hPTHR1s can stimulate both PLC and PKCs when activa ted by C-terminally truncated fragments of PTH(1-31). Furthermore, hPTHR1s, like the PTHR1s in rat osteoblasts, opossum kidney cells, and rat PTHR1-tr ansfected CHO cells also can stimulate PKC activity by a mechanism that is independent of PLC. The efficiency with which the N-terminally truncated PT H peptides stimulate PKC activity depends on the cellular context in which the PTHR1s are expressed.