20.4 Response to the Signal

Cells respond to the activation of receptors by their ligands in a variety of different ways. The results of signaling pathways are extremely varied and depend on the type of cell involved as well as the external and internal conditions. A small sampling of responses is described below.

Gene Expression

Some signal transduction pathways regulate the transcription of specific genes. This could be through the activation of transcription factors through phosphorylation or activation of second messengers. In quorum sensing, some autoinducers are hydrophobic in nature and will bind to cytoplasmic receptors (e.g., luxR). Once bound to its ligand, the luxR receptor can bind to specific sequences in the DNA and trigger transcription of both the luxR gene itself and the luxICDABEG operon (Figure 1). This results in higher expression of the luxR receptor (positive feedback) and expression of the proteins required to produce the luciferase protein. Note that luxI is an inhibitor of the autoinducer, which ensures termination of the signal (negative feedback).

Figure 1. Activation of the lux operon by LuxR and LuxI in Aliivibrio fischeri. (A) At low cell density, the autoinducers (3OC6-HSL – red dots), produced by LuxI, diffuse through the cell membrane into the growth medium. (B) As the cell growth continues, the autoinducers in the medium start to accumulate in a confined environment. A very low intensity of light can be detected. (C) When enough autoinducers have accumulated in the medium, they can re-enter the cell where they directly bind the LuxR protein to activate luxICDABEG expression. (D) High levels of autoinducers activate the luminescent system of A. fischeri. A high intensity of light can be detected. Based on Li and Nair (2012) (authorization of use license number 4454260086749).

Increase in Cellular Metabolism

Signaling pathways can also influence cellular metabolism. This is primarily through enhancing or inhibiting the activities of metabolic proteins that are responsible for extracting energy from nutrients in the environment or modulate the ability to take up those same nutrients into the cell. A good example of this kind of signaling pathway that also involves transcriptional regulation, is the signaling pathway downstream of the lactose permease discussed in Section 19.1 Transcriptional Regulation of the Lac operon.

Cell Growth

Cell signaling pathways also play a major role in cell division. Cells do not normally divide unless they are stimulated by signals from other cells. The ligands that promote cell growth are called growth factors. Most growth factors bind to cell-surface receptors that are linked to tyrosine kinases. These cell-surface receptors are called receptor tyrosine kinases (RTKs). Activation of RTKs initiates a signaling pathway that then stimulates the expression of proteins that interact with other cellular components to initiate cell division.

Cell Death

Termination of the Signal Cascade

The aberrant signaling often seen in tumor cells is proof that the termination of a signal at the appropriate time can be just as important as the initiation of a signal. One method of stopping a specific signal is to degrade the ligand or remove it so that it can no longer access its receptor. One reason that hydrophobic hormones like estrogen and testosterone trigger long-lasting events is because they bind carrier proteins. These proteins allow the insoluble molecules to be soluble in blood, but they also protect the hormones from degradation by circulating enzymes.

Inside the cell, many different enzymes reverse the cellular modifications that result from signaling cascades. For example, phosphatases are enzymes that remove the phosphate group attached to proteins by kinases in a process called dephosphorylation. Cyclic AMP (cAMP) is degraded into AMP by phosphodiesterase, and the release of calcium stores is reversed by the Ca²⁺ pumps that are located in the external and internal membranes of the cell.