PTH receptor coupling to phospholipase C is an alternate pathway of signal transduction in bone and kidney.
The parathyroid hormone (PTH) receptor is coupled via a guanine nucleotide-binding regulatory protein (G protein) to phospholipase C (PLC). Binding of PTH to its receptor leads to activation of PLC with the subsequent hydrolysis of phosphatidylinositol 4,5-bisphosphate to inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 generation leads to the release of intracellular calcium stores, which produces an increase in the intracellular calcium concentration. DAG activates protein kinase C (PKC). Both IP3 metabolites and PKC may play a role in returning the intracellular calcium concentration back to base line, by stimulating the movement of calcium from the intracellular to the extracellular compartment, as well as by sequestering calcium within intracellular organelles. PKC appears to be important in the development of desensitization and downregulation of the PTH receptor to PTH. Activation of PLC may be important in modulating the well-known effects of PTH on bone and kidney and also may be relevant to recently described actions, such as the possible role of PTH as a growth factor in skeletal tissue. Important issues that need to be addressed in this field include 1) characterization of the PTH receptor, 2) the possible role of low-molecular-weight G proteins in PTH signal transduction, and 3) further description of the role of alternate pathway signal transduction in producing the effects of PTH.
Dunlay
R
R
Department of Medicine, Jewish Hospital, Washington University, St. Louis, Missouri 63110.
Hruska
K
K
D000818:Animals; D001842:Bone and Bones / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018016:Receptors, Parathyroid Hormone; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism*
D010281:Parathyroid Hormone; D010716:Phosphatidylinositols; D011956:Receptors, Cell Surface; D018016:Receptors, Parathyroid Hormone; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins