Signal Transduction Tutorial
The goal of this tutorial is for you to gain an understanding of how cell signaling occurs in a cell. Upon completion of the tutorial, you will have a basic understanding signal transduction and the role of phosphorylation in signal transduction. You will also have detailed knowledge of the role of Tyrosine kinases and G protein-coupled receptors in cell signaling.
Complete all three portions of this tutorial:
As living organisms we are constantly receiving and interpreting signals from our environment. These signals can come in the form of light, heat, odors, touch or sound. The cells of our bodies are also constantly receiving signals from other cells. These signals are important to keep cells alive and functioning as well as to stimulate important events such as cell division and differentiation.
Signals are most often chemicals that can be found in the extracellular fluid around cells. These chemicals can come from distant locations in the body (endocrine signaling by hormones), from nearby cells (paracrine signaling) or can even be secreted by the same cell (autocrine signaling).
Signaling molecules may trigger any number of cellular responses, including changing the metabolism of the cell receiving the signal or result in a change in gene expression (transcription) within the nucleus of the cell or both.
Cell signaling can be divided into 3 stages.
1. Reception: A cell detects a signaling molecule from the outside of the cell. A signal is detected when the chemical signal (also known as a ligand) binds to a receptor protein on the surface of the cell or inside the cell.
2. Transduction: When the signaling molecule binds the receptor it changes the receptor protein in some way. This change initiates the process of transduction. Signal transduction is usually a pathway of several steps. Each relay molecule in the signal transduction pathway changes the next molecule in the pathway.
3. Response: Finally, the signal triggers a specific cellular response.
Membrane receptors function by binding the signal molecule (ligand) and causing the production of a second signal (also known as a second messenger) that then causes a cellular response. These type of receptors transmit information from the extracellular environment to the inside of the cell by changing shape or by joining with another protein once a specific ligand binds to it. Examples of membrane receptors include G Protein-Coupled Receptors and Receptor Tyrosine Kinases.
Intracellular receptors are found inside the cell, either in the cytopolasm or in the nucleus of the target cell (the cell receiving the signal). Chemical messengers that are hydrophobic or very small (steroid hormones for example) can pass through the plasma membrane without assistance and bind these intracellular receptors. Once bound and activated by the signal molecule, the activated receptor can initiate a cellular response, such as a change in gene expression.
Since signaling systems need to be responsive to small concentrations of chemical signals and act quickly, cells often use a multi-step pathway that transmits the signal quickly, while amplifying the signal to numerous molecules at each step.
Steps in the signal transduction pathway often involve the addition or removal of phosphate groups which results in the activation of proteins. Enzymes that transfer phosphate groups from ATP to a protein are called protein kinases. Many of the relay molecules in a signal transduction pathway are protein kinases and often act on other protein kinases in the pathway. Often this creates a phosphorylation cascade, where one enzyme phosphorylates another, which then phosphorylates another protein, causing a chain reaction.
Also important to the phosphorylation cascade are a group of proteins known as protein phosphatases. Protein phosphatases are enzymes that can rapidly remove phosphate groups from proteins (dephosphorylation) and thus inactivate protein kinases. Protein phosphatases are the "off switch" in the signal transduction pathway. Turning the signal transduction pathway off when the signal is no longer present is important to ensure that the cellular response is regulated appropriately. Dephosphorylation also makes protein kinases available for reuse and enables the cell to respond again when another signal is received.
Kinases are not the only tools used by cells in signal transduction. Small, nonprotein, water-soluble molecules or ions called second messengers (the ligand that binds the receptor is the first messenger) can also relay signals received by receptors on the cell surface to target molecules in the cytoplasm or the nucleus. Examples of second messengers include cyclic AMP (cAMP) and calcium ions.
Cell signaling ultimately leads to the regulation of one or more cellular activities. Regulation of gene expression (turning transcription of specific genes on or off) is a common outcome of cell signaling. A signaling pathway may also regulate the activity of a protein, for example opening or closing an ion channel in the plasma membrane or promoting a change in cell metabolism such as catalyzing the breakdown of glycogen. Signaling pathways can also lead to important cellular events such as cell division or apoptosis (programmed cell death).
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G- Protein-Coupled Receptor
Receptor Tyrosine Kinase
Signal Transduction Tutorial by Dr. Katherine Harris is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
Funded by the U.S. Department of Education, College Cost Reduction and Access (CCRAA) grant award # P031C080096.