Steroid hormone receptor Phosphorylation

Steroid hormone receptors are phosphoproteins that have a DNA-binding domain and a steroid-binding domain. All steroid receptors have a molecular weight of 55,000-120,000. The state of phosphorylation appears to influence functional activity. 

Furthermore, post-translational modifications activate steroid hormone receptors in a ligand-independent fashion (Fig. 5), as shown for the ERa which is phosphorylated on serine residue 118 in the AF-1 domain by the Erkl/2 kinase [71]. In vitro, the serine-118 phosphorylated ERa is transcriptionally active in a ligand-independent fashion. 

The steroid hormone receptors are phophoproteins which are usually phosphorylated on several positions. The phosphorylation sites are mainly foimd in the N-terminal region of the receptors. Serine phosphorylation prevails. One rare example of tyrosine phosphorylation is described for the case of estrogen receptors. The consequences of phosphorylation for the receptor proteins are varied. It is conceivable, and in some cases experimentally proven, that it has influence on hormone binding, nuclear transport, DNA binding and transactivation. 

Modulator of steroid-hormone receptor binds with hsp90, GC receptor and dynein at different sites phosphorylated by casein kinase II. 

Hormonal actions on target neurons are classified in terms of cellular mechanisms of action. Hormones act either via cell-surface or intracellular receptors. Peptide hormones and amino-acid derivatives, such as epinephrine, act on cell-surface receptors that do such things as open ion-channels, cause rapid electrical responses and facilitate exocytosis of hormones or neurotransmitters. Alternatively, they activate second-messenger systems at the cell membrane, such as those involving cAMP, Ca2+/ calmodulin or phosphoinositides (see Chs 20 and 24), which leads to phosphorylation of proteins inside various parts of the target cell (Fig. 52-2A). Steroid hormones and thyroid hormone, on the other hand, act on intracellular receptors in cell nuclei to regulate gene expression and protein synthesis (Fig. 52-2B). Steroid hormones can also affect cell-surface events via receptors at or near the cell surface. 

K22. Kuiper G. G., de Ruiter, P. E., and Brinkmann, A. O., Androgen receptor heterogeneity in LNCaP cells is caused by a hormone independent phosphorylation step. J. Steroid Biochem. Mol. Biol. 41, 697-700 (1992). 

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