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 × 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. © 1996, Government of Canada. Exclusive worldwide publication rights in the article have been transferred to Wiley‐Liss, Inc., in perpetuity.