cell signaling

Cell Signaling Basics

1. Cell signaling in animal cells involve communication by direct contact between cells or by sending signal molecules across short or long distances between cells 

2. There are three stages of cell signaling:

• Reception – the target cell’s detection of a signal molecule coming from outside the cell

• Transduction – the conversion of the signal to a form that can cause a specific cellular response

• Response – the specific cellular response to the signal molecule

Reception: a signaling molecule binds to a receptor protein, causing it to change shape

3. The binding of a signaling molecule (ligand) to a receptor is highly specific (i.e. each receptor is shaped to match exactly with a particular ligand).  Once the ligand is bound to the receptor, this may cause a shape change in the receptor.  This shape change in the receptor is considered the first step of transduction. 

4. Types of Receptors: Intracellular (found inside the cell membrane in the cytoplasm or nucleus and Plasma Membrane Receptors (found on the surface of the cell membrane) 

5. Example Receptor #1: G-Protein Coupled Receptor (in other words, a membrane receptor that uses a G protein)  

• Step 1: 

• a ligand binds to the receptor and changes its shape

• the receptor binds to a G protein

• the G protein replaces GDP (like ADP) with GTP (like ATP), and the G protein is then activated

• Step 2: 

• the G protein binds to an enzyme and activates it 

• the enzyme triggers the next step leading to a cell response

• This activation of the G protein is temporary…to continue the response, new signal molecules are required

• A real example of the use of a G protein in your body is given below.  The lettered steps correspond to the letters in the diagram on the next page. 

1. Epinephrine (one of the only chemicals classified as a neurotransmitter AND a hormone) is released from glands sitting on top of your kidneys called the adrenal glands.

2. Epinephrine travels throughout the bloodstream and binds to G-protein coupled receptor on the surface of a liver cell.  

3. The G-protein coupled receptor changes shape and results in the activation of its attached G protein (how the G protein is activated with GTP is described above under Step 1!)

4. A portion of the G protein called the alpha subunit detaches and activates another protein in the cell membrane called adenylyl cyclase.  This protein is an enzyme and, once activated, it converts ATP to cAMP, or cyclic AMP.  (Cyclic AMP is basically like ATP, but with only one phosphate group and in the shape of a ring).

Cyclic AMP (cAMP) is considered a “second messenger” because it takes the message from the original messenger molecule / ligand (in this case epinephrine) and converts it to a form that the cell can respond to.  Second messengers (like cAMP, cyclic GMP, IP₃, and Ca²⁺) amplify the signal because many second messenger molecules can be created from a single original signal molecule (ex: epinephrine). 

5. Many cAMP molecules spread throughout the cell and activate protein kinases.  These kinases can then steal phosphate groups from ATP and can pass them to another protein enzyme called phosphorylase to activate it.

6. Once activated, phosphorylase begins chopping glucose monomers off of glycogen (a large storage polysaccharide in the cell).  

7. The glucose monomers are released from the liver cell into the bloodstream.  These glucose monomers can be used as fuel/energy for your muscle cells, which must be used in the “fight or flight response” that results from epinephrine secretion, which occurs when you are afraid.  

6. Example Receptor #2: Receptor Tyrosine Kinase (Note: Both types of receptors I am describing—G-protein coupled receptors and receptor tyrosine kinases—are examples of plasma membrane receptors, not intracellular receptors.) 

• Step 1: 

• two signal molecules bind to two receptors, which come together to form a “dimer receptor” (di = two) 

• the dimer formation allows tyrosine kinases to “steal” phosphate groups from ATP, and the tyrosine kinases are now activated

• Step 2: 

• each phosphorylated receptor tyrosine kinase can begin a cellular response by activating “relay” (messenger) proteins by donating the active phosphate group to them

7. Typically, large, polar, or charged signal molecules bind to plasma membrane receptors because they cannot pass through the cell membrane to get to intracellular receptors.  For example, epinephrine is an amine hormone, which is derived from the amino acid tyrosine.  It is polar, so it is unable to pass through the non-polar tail region of the cell membrane. 

8. Typically, small, non-polar signal molecules bind to intracellular receptors (i.e. receptors found inside the cell) because they can pass through the cell membrane (specifically the non-polar tail region) on their own.  For example, steroid hormones like testosterone are non-polar. 

Transduction: chain reactions between many molecules result in the sending of a signal from the receptors to target molecules in the cell

9. Signal transduction pathways often involve a phosphorylation cascade 🡪 where protein kinases phosphorylate MANY proteins at the next step to activate them 🡪 the signal gets amplified!

10. The above example of the use of cAMP as a second messenger for the epinephrine ligand represents signal transduction as well.  The signal from epinephrine is converted or “transduced” into a different form (MANY cyclic AMP molecules) and the signal is amplified!

11. Signals can be turned off by protein phosphatases that remove phosphate groups from proteins in the cascade