Parathyroid hormone stimulates protein kinase C but not adenylate cyclase in mouse epidermal keratinocytes

Abstract

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.

Ca2+·Calmodulin Prevents Myristoylated Alanine-rich Kinase C Substrate Protein Phosphorylation by Protein Kinase Cs in C6 Rat Glioma Cells

“…1B). We have previously shown that the Ac-FKKSFKL-NH 2 phosphorylating activity in membranes from several types of cells is that of PKCs (Chakravarthy et al, 1991Whitfield et al, 1992). The same was true for C6 glioma cell membrane-associated protein kinase activity.…”

“…Direct Measurement of Membrane-associated PKC Activity-Membrane-associated PKCs activity was measured directly in isolated membranes (without prior extraction and reconstitution of the enzyme in artificial phopholipid membranes) by determining the incorporation of 32 P into a PKC-selective peptide substrate, Ac-FKKSFKL-NH 2 (Chakravarthy et al, 1991(Chakravarthy et al, , 1994Whitfield et al, 1992). This peptide corresponds to residues 160 -166 of the phosphorylation site domain (151-175) of the MARCKS protein, a specific cellular substrate of PKC (Aderem, 1992;Blackshear, 1993).…”

“…Pretreating the glioma cells with ionomycin prevented TPA-stimulated PKCs from phosphorylating the MARCKS protein. but raising the Ca 2ϩ concentration above 1 mM stops proliferation and starts differentiation-related processes such as cornified envelope formation Falco et al, 1988;Moscat et al, 1989; Aaroson, 1983, 1985;Whitfield, 1995;Whitfield et al, 1992Whitfield et al, , 1995. The signal triggered by extracellular Ca 2ϩ in murine BALB/MK keratinocytes includes an internal Ca 2ϩ transient and a large burst of membrane-associated PKCs activity .…”

C‐terminal fragments of parathyroid hormone‐related protein, PTHrP‐(107‐111) and (107‐139), and the N‐terminal PTHrP‐(1‐40) fragment stimulate membrane‐associated protein kinase C activity in rat spleen lymphocytes

“…Some support for this suggestion is provided by evidence indicating that PTH is a wound hormone which is released from the parathyroid glands in response to surgical and other injuries, to stimulate an immune response and promote hemopoiesis presumably by activating PTHIPTHrP receptors on precursor cells (Whitfield, 1990;Whitfield et al, 1992). Indeed, PTH stimulates the proliferation of rat thymic lymphoblasts and bone marrow CFU-S progenitor cells, enhances the phytohemagglutinin-induced expression of interleukin-2 (IL-2) receptors and the proliferation of human peripheral blood T lymphocytes, and promotes the primary immune response in rats to the injection of sheep red blood cells (Atkinson et al, 1987;Klinger et al, 1990;Swierenga et al, 1976;Whitfield, 1990Whitfield, ,1992Whitfield et al, 1971Whitfield et al, ,1992. PTHrP holoprotein and Nand/or C-terminal PTHrP fragments generated by local proteases might be potent autocrine or paracrine modulators of the proliferation of both normal lymphocytes and lymphocytes in PTHrP-expressing tumors.…”

Na/H Exchanger Regulatory Factors Control Parathyroid Hormone Receptor Signaling by Facilitating Differential Activation of Gα Protein Subunits

“…In some cases, occupancy of the PTHR activates only one signaling pathway. For example, in vascular smooth muscle cells, PTH stimulates adenylyl cyclase but not PLC (3,4), whereas in keratinocytes (5,6), cardiac myocytes (7,8), and lymphocytes (9 -11), the PTHR activates PLC but not adenylyl cyclase. In osteoblasts and kidney tubule cells, PTH activates both adenylyl cyclase and PLC (12)(13)(14).…”