SIG - Introduction to Signal Transduction [LESSON]

Introduction of Signal Transduction

First, watch the Signal Transduction Pathways video below and take detailed notes about the basics of signal transduction pathways.

Just as a journey begins with a single step, a signaling pathway begins with a single key event – the binding of the signaling molecule (ligand) to the corresponding receptor protein. Receptor proteins and ligands come in closely matched pairs and a receptor will only recognize one or a few specific ligands. Remember that a cell needs to have a receptor protein of a specific shape in order to respond to a signal. Binding of a ligand to a receptor changes the shape of the receptor protein, which starts the next step of the pathway.

There are three major steps to any signal transduction pathway: reception, transduction, and cellular response. We will look at some common examples of things that can happen in each step during this lesson.

Reception

Receptors come in many types, but they can be divided into two categories: intracellular receptors, which are found inside of the cell (in the cytoplasm or nucleus), and cell surface receptors, which are found in the plasma membrane.

Cell-surface receptors are membrane-anchored proteins that bind to ligands on the outside surface of the cell. If a ligand is large and/or hydrophilic, then the receptor is typically embedded in the cell membrane. Binding of the ligand causes a change in the 3-D shape of the receptor protein inside the cell, activating the next step in the signaling pathway.  A special type of cell-surface receptor is the G-protein-coupled receptor. G protein-coupled receptors (GPCRs) are a large family of cell surface receptors that share a common structure and method of signaling. The members of the GPCR family all have seven different protein segments that cross the membrane, and they transmit signals inside the cell through a type of protein called a G protein (more details in the image below).  It is not required for you to memorize every detail of the GPCR pathway, but it is an important and very common receptor mechanism that you should be familiar with.

Receptor tyrosine kinases (RTKs) are a class of enzyme-linked receptors found in humans and many other species. A kinase is just a name for an enzyme that transfers phosphate groups to a protein or other target, and a receptor tyrosine kinase transfers phosphate groups specifically to the amino acid tyrosine. This is another very common example of a cell-surface receptor.

Intracellular receptors are receptor proteins found on the inside of the cell, typically in the cytoplasm or nucleus. In most cases, the ligands of intracellular receptors are small hydrophobic molecules, since they must be able to cross the plasma membrane in order to reach their receptors. A well-known example of this is testosterone, a steroid hormone.  Estrogen is also a steroid hormone that has an intracellular receptor.

Transduction

Transduction is the general term that describes the relay of signals inside a cell that will eventually produce a cellular response. There are many, many examples of different things that could happen during transduction. Remember, the receptor protein changes shape upon binding of the ligand and this will set off the transduction portion of the signaling pathway. 

• activation of another protein – one of the simplest examples would be that the next protein in the pathway is activated by the change in shape of the receptor protein.
• kinase/phosphatase – these are enzymes that phosphorylate or dephosphorylate other molecules which can activate or inactivate them.

• release of a second messenger – a second messenger is a molecule that is released during transduction that is NOT a protein but does pass along a signal.  The most common examples are calcium ions (Ca2+) released from an organelle into the cytoplasm and cyclic adenosine monophosphate (cAMP) which is converted from ATP in order to propagate the signal.  cAMP typically activates protein kinase A, which is a kinase that turns on lots of other proteins in order to amplify the signal quickly.

 

Now, walk through the steps of the Signal Transduction Example Pathway below by hovering over each area.

Cellular Response

Cell signaling pathways vary a lot. Signals (ligands) and receptors come in many varieties, and binding can trigger a wide range of signal relay cascades inside the cell, from short and simple to long and complex. Despite these differences, signaling pathways share a common goal which is to produce some kind of cellular response. There are two broad categories of cellular responses and each can change the cell at the microscopic or macroscopic level.

Option 1 is to activate or deactivate enzymes or other cellular proteins.  For example, epinephrine ligand will eventually turn on an enzyme called glycogen phosphorylase and turn off an enzyme called glycogen synthase. Both of these responses serve to ensure that glycogen is broken up instead of being formed during the fight or flight response that epinephrine release causes. We need lots of glucose, so we break down our glycogen reserves to obtain it!

Option 2 is to change gene expression of the cell in order to make new proteins (typically by activating a transcription factor). Transcription factors increase or decrease transcription of certain genes. For example, growth factor causes the activation of a transcription factor that makes new proteins that regulate cell division.

NOTE: There will be many complex diagrams such as the one below. You do NOT have to memorize specifics of any signaling pathways, but you do have to understand a diagram and predict changes to it.

Activation is indicated by an arrow.

Inhibition is indicated by a “T” at the end, such as

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