Activation of the Cytoplasmic Apo-Receptor Complexes

The steroid hormones are distributed throughout the entire organism by means of the circulatory system. Transport often occurs in the form of a complex with a specific binding protein. An example for such a binding protein is transcortin, which is responsible for the transport of the corticosteroids. The steroid hormones enter the cell by diffusion and activate the cytosolic receptors. 

In the absence of steroid hormones the receptors remain in an inactive complex, designated the apo-receptor complex (review Pratt, 1993 Bohen, 1995). In the apore-ceptor complex the receptor is boimd to proteins belonging to the chaperone class. Chaperones are proteins whose levels are increased as a result of a stress situation, such as a rise in ambient temperature. The chaperones assume a central function in the folding process of proteins in the cell. Chaperones aid proteins in avoiding incorrectly folded states. They participate in the folding of proteins during and after ribosomal protein biosynthesis, during membrane transport of proteins, as well as in the correct assembly of protein complexes. 

With the help of co-immimoprecipitation it could be shown that the receptors of steroid hormones interact with at least three chaperones, Hsp90, Hsp70 and Hsp56 (fig. 4.10). The term Hsp (Heat shock protein) is derived from the observation that these proteins were produced at higher levels following heat treatment. Furthermore, one finds a 23 kDa acidic protein in the apo-receptor complex whose fimction is not yet clear. 

It is assumed that the receptor, when complexed with Hsp90, Hsp56 and p23, is fixed in an optimal conformation for hormone binding. The activation of the receptor by the hormone requires the presence of Hsp90, which binds the receptor as a dimer. Hsp90 

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