Parathyroid hormone stimulates protein kinase C but not adenylate cyclase in mouse epidermal keratinocytes.
Intact human parathyroid hormone, hPTH [1-84], and the hPTH [1-34] fragment stimulated membrane-associated protein kinase C (PKC) activity in immortalized (but still differentiation-competent) murine BALB/MK-2 skin keratinocytes. Unexpectedly, the hormone and its fragment did not stimulate adenylate cyclase. The failure of PTH to stimulate adenylate cyclase activity was not due to the lack of a functioning receptor-cyclase coupling mechanism because the cells were stimulated to synthesize cyclic adenosine monophosphate (cyclic AMP) by the beta-adrenergic drug isoproterenol. Thus, skin keratinocytes seem to have an unconventional PTH receptor that is coupled to a PKC-activating mechanism but not to adenylate cyclase. These observations suggest that normal and neoplastic skin keratinocytes respond to the PTH-related peptide that they make and secrete.
Whitfield
J F
JF
Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario.
Chakravarthy
B R
BR
Durkin
J P
JP
Isaacs
R J
RJ
Jouishomme
H
H
Sikorska
M
M
Williams
R E
RE
Rixon
R H
RH
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D000078404:Epidermal Cells; D015603:Keratinocytes / Q000201:enzymology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D012516:Osteosarcoma / Q000378:metabolism; D010281:Parathyroid Hormone / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013329:Structure-Activity Relationship
D010281:Parathyroid Hormone; D010455:Peptides; D000242:Cyclic AMP; D011493:Protein Kinase C; D000262:Adenylyl Cyclases