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 β‐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.

[1]  M. Sikorska,et al.  The direct measurement of protein kinase C (PKC) activity in isolated membranes using a selective peptide substrate. , 1991, Analytical biochemistry.

[2]  F. Marks,et al.  Protein kinase C activation by phorbol esters: do cysteine-rich regions and pseudosubstrate motifs play a role? , 1991, Trends in biochemical sciences.

[3]  T. Martin.  Receptor regulation of phosphoinositidase C. , 1991, Pharmacology & therapeutics.

[4]  J. Durkin,et al.  Parathyroid hormone fragment [3-34] stimulates protein kinase C (PKC) activity in rat osteosarcoma and murine T-lymphoma cells. , 1990, Biochemical and biophysical research communications.

[5]  J. Whitfield.  Calcium, cell cycles, and cancer , 1990 .

[6]  D. Franks,et al.  Protein kinase C and a viral K‐RAS protein cooperatively enhance the response of adenylate cyclase to stimulators , 1989, Journal of cellular physiology.

[7]  J. Graff,et al.  Characterization of the phosphorylation sites in the chicken and bovine myristoylated alanine-rich C kinase substrate protein, a prominent cellular substrate for protein kinase C. , 1989, The Journal of biological chemistry.

[8]  J. Hayman,et al.  Parathyroid hormone‐related protein: Immunohistochemical localization in cancers and in normal skin , 1989, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[9]  S. Yuspa,et al.  Intracellular calcium alterations in response to increased external calcium in normal and neoplastic keratinocytes. , 1989, Carcinogenesis.

[10]  D. Roop,et al.  Signal Transduction for Proliferation and Differentiation in Keratinocytes , 1988, Annals of the New York Academy of Sciences.

[11]  M. Centrella,et al.  Characterization of a parathyroid Hormonelike Peptide Secreted by Human Keratinocytes , 1988, Annals of the New York Academy of Sciences.

[12]  A. Budayr,et al.  Evidence that parathyroid hormone-mediated calcium transport in rat brain synaptosomes is independent of cyclic adenosine monophosphate. , 1988, The Journal of clinical investigation.

[13]  S. Yuspa,et al.  Chemical carcinogenesis: from animal models to molecular models in one decade. , 1988, Advances in cancer research.

[14]  B. Kemp,et al.  Protein kinase C contains a pseudosubstrate prototope in its regulatory domain. , 1987, Science.

[15]  M. Atkinson,et al.  Parathyroid hormone stimulation of mitosis in rat thymic lymphocytes is independent of cyclic AMP , 1987, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[16]  A. Gilman,et al.  G proteins: transducers of receptor-generated signals. , 1987, Annual review of biochemistry.

[17]  D. Bikle,et al.  1,25-Dihydroxyvitamin D3 production by human keratinocytes. Kinetics and regulation. , 1986, The Journal of clinical investigation.

[18]  B. Weissman,et al.  Members of the src and ras oncogene families supplant the epidermal growth factor requirement of BALB/MK-2 keratinocytes and induce distinct alterations in their terminal differentiation program , 1985, Molecular and cellular biology.

[19]  B. Weissman,et al.  BALB and kirsten murine sarcoma viruses alter growth and differentiation of EGF-dependent BALB/c mouse epidermal keratinocyte lines , 1983, Cell.

[20]  S. Krane,et al.  Parathyroid hormone inhibitors: comparison of biological activity in bone- and skin-derived tissue. , 1979, The Journal of clinical endocrinology and metabolism.

[21]  M. M. Bradford.  A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[22]  D. Franks,et al.  The roles of calcium and cyclic AMP in the stimulatory action of parathyroid hormone on thymic lymphocyte proliferation , 1971, Journal of cellular physiology.