Hormone regulatory sites

HDC activity can be regulated by both hormonal and neuronal factors, most of which are poorly understood. Phosphorylation of the enzyme by PKA maybe an important regulatory mechanism. Several regulatory sites have recently been found in the promoter region of the gene. 

Ligand-bound corticosteroid receptors have been shown to interact to form heterodimers with other transcription factors, such as the jun protein. Such interactions are responsible for transactivation of the ds-regulatory sites known as AP-1 sites and for the glucocorticoid-mediated suppression of transcription, such as that seen in the pro-opiomelanocortin gene. A number of such specific protein interactions have been reported these interactions and their locations relative to other transcription factors transform a ubiquitous steroid hormone signal into a tissue-specific, graded cellular response. 

A number of regulatory enzymes have a serine (or sometimes a tyrosine or threonine) residue at a regulatory site. This can undergo phosphorylation catalysed by a protein kinase, as shown in Figure 10.5. Phosphorylation may increase or decrease the activity of the enzyme. Later, the phosphate group is removed from the enzyme by phosphoprotein phosphatase, thus restoring the enzyme to its original state. These responses are not instantaneous, but they are rapid, with a maximum response within a few seconds of hormone stimulation. 

Adenylyl Cyclases. Figure 4 Regulation of adenylyl cyclases by G-proteins. Abbreviations Hs, Hj, Rs, and Rj denote hormones and receptors that lead to stimulation or inhibition, respectively, of adenylyl cyclases, Ca and Ci are active and inactive configurations of adenylyl cyclase, Fo forskolin binding site, Gs and Gj are GTP-dependent regulatory proteins comprising their respective as, and (3y subunits. 

Heterodimerization of receptor molecules is a mechanism that can increase and modulate the diversity and regulation of signal transduction pathways. Since the various members of a receptor family differ in the exact structure of the autophosphorylation sites and the other regulatory sequences, it is assumed that activity and regulation are different for the various combinations of receptor subtypes. Tissue-specific expression of receptor subtypes enables the organism to process growth hormone signals in a differential way. 

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