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
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
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.