1. 11.3 Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell  Signal transduction usually involves multiple steps and molecules.  Steps often include activation of proteins by addition or removal of phosphate groups or release of other small molecules or ions.  Benefits of multistep pathways:  Amplification of response  More opportunities for coordination and regulation

2. Signal Transduction Pathways  The binding of a specific signaling molecule to a receptor in the plasma membrane triggers the first step in the signal transduction pathway.  The molecules that relay a signal from receptor to response are mostly proteins.  The original signaling molecule is not physically passed along the pathway, only the information is passed on.  At each step, the signal is transduced into a different form, usually a shape change in a protein.

3. Protein Phosphorylation and Dephosphorylation  In many pathways, the signal is transmitted by a cascade of protein phosphorylations.  Protein kinases transfer phosphates from ATP to protein, a process called phosphorylation.  Cytoplasmic protein kinases phosphorylate serine or threonine.  Usually phosphorylation activates a protein.  Protein phosphatases remove the phosphates from proteins, a process called dephosphorylation.  Usually dephosphorylation inactivates a protein (when signal is no longer present).  Phosphatases also make the protein kinases available for resuse. ***This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off or up or down, as required.

4. Small Molecules and Ions as Second Messengers  The extracellular signal molecule (ligand) that binds to the receptor is a pathway’s “first messenger.”  Second messengers are small, nonprotein, water-soluble molecules or ions that spread throughout a cell by diffusion.  Second messengers participate in pathways initiated by GPCRs and RTKs.  Cyclic AMP and calcium ions are common second messengers.

5. Cyclic AMP Cyclic AMP (cAMP) is one of the most widely used second messengers. Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal. An enzyme, called phosphodiesterase, converts cAMP to AMP in the absence of an extracellular signal. Adenylyl cyclase Phosphodiesterase Pyrophosphate AMP H2OH2O ATP P i P cAMP

6. Calcium Ions and Inositol Triphosphate (IP 3 )  Calcium ions (Ca 2+ ) act as a second messenger in many pathways.  Increase cytosolic concentration of Ca 2+ causes many responses in animal cells (muscle cell contraction, secretion, and cell division).  Cells use Ca 2+ as a second messenger in pathways triggered by both GPCRs and RTKs.  Calcium is an important second messenger because cells can regulate its concentration.  Under normal conditions, the concentration of Ca 2+ in the cytoplasm is lower than outside the cell and in the ER.  A signal relayed by a signal transduction pathway may trigger an increase in calcium in the cytosol.  Pathways leading to the release of calcium involve inositol triphosphate (IP 3 ) and diacylglycerol (DAG) as additional second messengers.