C-terminal fragment of parathyroid hormone-related protein, PTHrP-(107-111), stimulates membrane-associated protein kinase C activity and modulates the proliferation of human and murine skin keratinocytes.
Low concentrations of the C-terminal parathyroid hormone-related protein (PTHrP) fragments, PTHrP-(107-111) and PTHrP-(107-139), stimulated membrane-associated protein kinase Cs (PKCs), but not adenylyl cyclase or an internal Ca2+ surge, in early passage human skin keratinocytes and BALB/MK-2 murine skin keratinocytes. The fragment maximally stimulated membrane-associated PKCs in BALB/MK-2 cells at 5 x 10(-9) to 10(-8) M. The maximally PKC-stimulating concentrations of PTHrP-(107-111) also stopped or stimulated BALB/MK-2 keratinocyte proliferation depending on whether the cells were, respectively, cycling or quiescent at the time of exposure. Thus, just one brief (30-minute) pulse of 10(-8) M PTHrP-(107-111) stopped the proliferation of BALB/MK-2 keratinocytes for at least 5 days. On the other hand, daily 30-minute pulses of 10(-8) M PTHrP-(107-111) started and then maintained the proliferation of initially quiescent BALB/MK-2 cells. Similarly PTHrP-(107-111) inhibited DNA synthesis by cycling primary adult human keratinocytes, but it stimulated DNA synthesis by quiescent human keratinocytes.
Whitfield
J F
JF
Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada.
Isaacs
R J
RJ
Jouishomme
H
H
MacLean
S
S
Chakravarthy
B R
BR
Morley
P
P
Barisoni
D
D
Regalia
E
E
Armato
U
U
D000262:Adenylyl Cyclases / Q000378:metabolism; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured / Q000166:cytology / Q000201:enzymology; D003470:Culture Media; D000078404:Epidermal Cells; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000201:enzymology*; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010281:Parathyroid Hormone / Q000502:physiology*; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000502:physiology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D011506:Proteins / Q000502:physiology*; D013696:Temperature; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014316:Tritium
D003470:Culture Media; D008565:Membrane Proteins; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; C071784:parathyroid hormone-related protein (107-111); D014316:Tritium; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D002118:Calcium; D013936:Thymidine