Surface Receptors Linked Directly to Enzymes

It appears that insulin and certain growth factors may exert their effects by acting through this type of tyrosine kinase receptor-enzyme system.21,44 Insulin, for example, binds to the extracellular component of a protein located on skeletal muscle cells, thereby initiating activation of this protein s enzymatic activity on the inner surface of the cell membrane. This change in enzyme function causes further changes in cell activity, which ultimately result in increased glucose uptake in the muscle cell. The function of insulin receptors and their role in the cause and treatment of diabetes mellitus are discussed in more detail in Chapter 32. 

Surface Receptors Linked to Regulatory (G) Proteins Role of the Second Messenger 

Rather than direcdy affecting membrane permeability or directly influencing enzyme activity, other membrane receptors affect cell function by linking to an intermediate regulatory protein that is located on the inner surface of the cell s membrane.2,23,45 These regulatory proteins are activated by binding guanine 

FIGURE 4-2 Example of a surface receptor that is linked directly to intracellular enzyme activity. (A) The receptor exists in an inactive state as two subunits each subunit has a binding domain (BD] on the outer surface and a catalytic domain CCD] on the inner surface. (B] Binding of agonist molecules to the BDs causes the subunits to join together and induces phosphorylation [P] of tyrosine receptors on the CD. Tyrosine phosphorylation initiates enzymatic activity of the catalytic units, which then causes substrate activation within the cell. 

Receptors that are linked to G proteins (also called G protein-coupled receptors) represent the primary way that signals from the surface receptor are transduced into the appropriate response within the cell.2,23 There appear to be two types of regulatory G proteins a stimulatory protein (Gs), which increases the cellular response, and an inhibitory protein (G ), which decreases that response (Fig. 4—3). The two types of G proteins are linked to two different receptors that are responsive to different drugs. 

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