Signal transduction hormone-receptor complexes

Signal pathways commonly amplify the initial signal received by the receptor during the course of the signal transduction (Fig. 3.10). In many cases only a few molecules of a hormone are sufficient to initiate an enzymatic reaction in a cell, in which many substrate molecules are turned over. The extent of amplification, or amplification factor, varies greatly at the different levels of the signal transmission. An initial amplification often occurs at the level of the hormone-receptor complex. An activated receptor is capable of activating many downstream effector proteins. 

Several studies have highlighted the importance of multidomain FKBPs in the control of signal transduction pathways. For example, hFKBP51 and hFKBP52 have been found in steroid hormone receptor complexes and are thought to play an important role in complex formation and translocation of receptor-ligand complexes from the cytosol into the nucleus [82,83], Notably, these multidomain FKBPs share structural characteristics as demonstrated by an N-terminal PPIase... 

The most common secondary messengers in signal transduction pathways, formed from the primary interaction, are calcium ions (Ca ). The receptor-hormone complex induces changes in the cell s metabolism, usualfy by affecting transcription or translatioiL... 

Fig. 4.4. The principle of signal transduction by nuclear receptors. Nuclear receptors are ligand-controlled transcription factors that bind cognate DNA sequences, or hormone responsive elements (HRE). The hormone acts as a regulating ligand. Most nuclear receptors bind their cognate HREs, which tend to be symmetrically organized, as homo- or heterodimers. The DNA-bound, activated receptor stimulates transcription initiation via direct or indirect protein-protein interactions with the transcription initiation complex. The arrows demonstrate the different possible configurations of the HRE (see also 4.6). H hormone Hsp heat shock protein.

Fig. 4.10. Principle of signal transduction by steroid hormone receptors. The steroid hormone receptors in the cytosol are found in the form of an inactive complex with the heat shock proteins Hsp90 and Hsp56 and with protein p23. The binding of the hormone activates the receptor so that it can be transported into the nucleus where it binds to its cognate HRE. It remains unclear in which form the receptor is transported into the nucleus, and to which extent the associated proteins are involved in the transport. One mechanism of activation of transcription initiation involves activation of a histone acetylase and remodehng of chromatin. Furthermore, the receptors interact directly or indirectly with components of the RNA polymerase II holoenzyme (e.g. SUGl).

A recently identified thyroid hormone cell surface receptor on the extracellular domain of integrin alphaVbeta (3) leads to the activation of the mitogen-activated protein kinase (MAPK) signal transduction cascade in human cell lines, Examples of MAPK-dependent thyroid hormone actions are plasma membrane ion pump stimulation and specific nuclear events, These events include serine phosphorylation of the nuclear thyroid hormone receptor, leading to co-activator protein recruitment and complex tissue responses, such as thyroid hormone-induced angiogenesis, The existence of this cell surface receptor means that the activity of the administered hormone could be limited through structural modification of the molecule to reproduce only those hormone actions initiated at the cell surface (8,9). 

Plasma membrane receptors are critical to the process of transmitting the information carried by the ligand or first messenger (neurotransmitter, hormone, etc.) from the extracellular space to the cell interior. However, cell signaling requires information flow inside the cell too. The molecules that carry this information to modulate the activity of ion channels, enzymes or receptors are sometimes referred to as second messengers. However, due to the complexity of signal transduction... 

Fig. 4.13 Principle of signal transduction by steroid hormone receptors. The steroid hormone receptors in the cytosol are found in the form of an inactive complex with the heat shock proteins Hsp90 and Hsp56 and with protein p23. The binding ofthe hormone activates the receptor so that it can be transported into the nucleus where it can...

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