M to 1.0 pM. The ability
of a tissue to respond to hormonal stimulation is a function of
the receptor density of cells in that tissue.
All known hormones interact with target
cells by initially binding to a macromolecular receptor, located
in either the plasma membrane or the interior of the cell. Because
the receptor participates in transduction of the signal from the
external messenger to some component of the metabolic machinery,
it must have at least one additional functional site. The activity
of this site is altered by hormone binding, just as the catalytic
site of an allosteric enzyme is altered by the binding of effectors
at remote sites. Most hormones bind tightly, with dissociation
constants in the range of 0.1 M to 1.0 pM. The ability
of a tissue to respond to hormonal stimulation is a function of
the receptor density of cells in that tissue.
There are three major classes of membrane-bound hormone receptors as follows:
1. Receptors that interact with G proteins and influence the synthesis of second messengers (See Figure 12.13, and here). Peptide hormones and epinephrine interact with this type of receptor.
2. Receptors that form ion channels--comparable to the nicotinic acetylcholine receptor (Figure 21.34). Peptide hormones and epinephrine interact with this type of receptor.
3. Receptors that are a transmembrane protein with a ligand-binding site on the extracellular side and a catalytic domain on the cytosolic side. In the insulin receptor, for example, the catalyst is a protein tyrosine kinase, which is stimulated by insulin binding to the extracellular domain of the receptor.
Mechanisms of hormones that act through membrane-bound receptors by the first and third mechanisms are summarized in Figure 23.7.
The end result of most interactions between a hormone and a membrane receptor is activation of one or more protein kinases, whether or not a second messenger is involved. More than 100 different protein kinases have been described in vertebrate cells, and all of them are related, as determined by amino acid sequence homologies. More recent work is uncovering a host of specific protein phosphatases, also subject to control by cell signaling mechanisms.
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