Cell Communication II PDF

Session Learning Outcomes (SLOs) SLO# 3: Describe the stages and events of cell signaling. SLO# 1 : Define kinases and phosphatases and their role in signal transduction.  The Three Stages of Cell Signaling Cells receiving signals went through three processes –...

Session Learning Outcomes (SLOs) SLO# 3: Describe the stages and events of cell signaling. SLO# 1 : Define kinases and phosphatases and their role in signal transduction.  The Three Stages of Cell Signaling Cells receiving signals went through three processes – Reception – Transduction – Response Called Signal transduction pathway Signal transduction: ability of cell to translate receptor- ligand interaction into a change in behavior or gene expression  Signal Transduction Pathway function: convert extracellular information into an appropriate cellular response composed of: – signals – receptors – signaling proteins – second messenger molecules Loading… EXTRACELLULAR CYTOPLASM FLUID Plasma membrane 1 Reception 2 Transduction 3 Response Recepto r Activation of cellular response Relay molecules in a signal transduction pathway Signaling molecule  The Three Stages of Cell Signaling 1) Reception: The target cell's detection of a signaling molecule coming from outside the cell. This occurs when a chemical signal is sensed due to the binding of a signaling molecule to a receptor protein, causing it to change shape. EXTRACELLULAR CYTOPLASM Loading… FLUID Plasma membrane 1 Reception Recepto r The receptor and signaling molecules fit together (lock and key model, induced fit model, just like enzymes) Signaling molecule  The Three Stages of Cell Signaling 2) Transduction: Transmission of the signal to effector molecules and down a signaling pathway where every protein typically changes the conformation of the next down the path, most commonly by phosphorylation (by kinases) or dephosphorylation (by phosphatases) EXTRACELLULAR CYTOPLASM FLUID Plasma membrane 1 Reception 2 Transduction Recepto r 2nd Messenger! Relay molecules in a signal transduction pathway Signaling molecule The signal is converted into a form that can produce a cellular response.  2. Transduction Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell Multistep pathways – Can amplify a signal (Amplifies the signal by activating multiple copies of the next component in the pathway) – Provide more opportunities for coordination and regulation Intracellular Key Concepts: signaling proteins propagate signals within a cell Signaling proteins rapidly transmit and amplify signal information. As information passes through a signal transduction pathway, it often changes physical form. Signaling proteins are grouped into six classes based on their structure, location, and mechanism of signal transmission. Second messengers are non-protein molecules that link signaling proteins together in signal transduction pathways.  Protein Phosphorylation and Dephosphorylation Many signal pathways – Include phosphorylation cascades – In this process, a series of protein kinases add a phosphate to the next one in line, activating it – Phosphatase enzymes then remove the phosphates  Protein Phosphorylation and Dephosphorylation Signal molecule Receptor Activated relay 1 A relay molecule molecule activates protein kinase 1. Tra Inactive Active protein kinase 1 nsd protein kinase 2 1 Active transfers a phosphate from ATP ucti Loading… protein kinase to an inactive molecule of on: 1 protein kinase 2, thus activating Inactive this second kinase. A protein kinase ATP ADP Active P 3 Active protein kinase 2 Phos 2 protein then catalyzes the phos- phory phorylation (and activation) oflation PP kinase Pi 2 Casca Inactive protein kinase 3. de protein kinase ATP 3 ADP Active P 4 Finally, active protein protein kinase 3 phosphorylates a 5 Enzymes called protein PP kinase phosphatases (PP) P i 3 protein that brings about the catalyze the removal of Inactive cell’s response to the signal. the phosphate groups protein ATP ADP P from the proteins, Active Cellular making them inactive protein response PP P and available for reuse. i  Many G-proteins trigger the formation of cAMP, which then acts as a second messenger in cellular pathways. First messenger (signal molecule such as epinephrine) Adenylyl G protein cyclase GTP G protein-coupled receptor ATP Second cAMP messenger Protein Transduction in a G- kinase A protein pathway Cellular responses  Small Molecules and Ions as Second Messengers Secondary messengers – Are small, nonprotein, water-soluble molecules or ions that act as secondary messengers.  The Three Stages of Cell Signaling 3) Response: The transduced signal triggers a specific cellular response. EXTRACELLULAR CYTOPLASM FLUID Plasma membrane 1 Reception 2 Transduction 3 Response Recepto r Activation of cellular response Relay molecules in a signal transduction pathway Signaling molecule The transduced signal triggers a cellular response 3. Response Response- cell signaling leads to regulation of transcription (turn genes on or off) or cytoplasmic activities. Animation of how epinephrine works - DnaTube.com - Scientific Video and Animation Site  Growth factor 3. Response Receptor Reception Many possible outcomes Phosphorylation cascade Transduction Ex: catalysis by an enzyme, rearrangement CYTOPLASM of the cytoskeleton, or activation of specific genes. Inactive transcription Active transcription factor factor Response P This example shows a DNA transcription response Gene NUCLEUS mRNA Four features of signal-transducing systems.  The Specificity of Cell Signaling Once a signaling molecule binds to its receptor it causes a conformational change in it that results in a cellular response. The same ligand can bind to the same receptor on different cell types causing different responses (e.g. acetylcholine). On the other hand, different ligands binding to different receptors can produce the same cellular response (e.g. glucagon, epinephrine).  The Specificity of Cell Signaling Different kinds of cells have different collections of proteins These differences in proteins give each kind of cell specificity in detecting and responding to signals The response of a cell to a signal depends on the cell’s particular collection of proteins Pathway branching and “cross-talk” further help the cell coordinate incoming signals  Specificity of the signal – The same signal molecule can trigger different responses – Many responses can come from one signal! Signaling molecule Recepto r The response of a particular cell to a signal Relay molecules depends on the type of proteins it contains. Response 1 Response 2 Response 3 Cell A. Pathway leads Cell B. Pathway branches, to a single response. leading to two responses.  The signal can also trigger an activator or inhibitor The signal can also trigger multiple receptors and different responses Activation or inhibition Response 4 Response 5 Cell C. Cross-talk occurs Cell D. Different receptor between two pathways. leads to a different response.  Termination of the Signal Signal response is terminated quickly – By the reversal of ligand binding https://youtu.be/zEZFl3MsmY0  Types of receptors In contrast to NO and the steroid and thyroid hormones, the vast majority of signal molecules are too large or too hydrophilic to cross the plasma membrane of the target cell. Most cell surface receptor proteins belong to on of three large families: 1.Ion channel-linked receptors, 2.G-protein-linked receptors, or 3.enzyme-linked receptors. Cell Surface Receptors differ in the nature of the intracellular signal that they generate when extracellular signal molecules binds to them. 1-ion-channel-linked receptors: the resulting signal is a flow of ions across the membrane, which produces electrical current. 2- G-protein-linked receptors activate a class of membrane bound proteins. 3- Enzyme-linked receptors act as an enzyme or are associated with enzymes inside the cell.  ion-channel-linked receptors Of all the cell-surface types, ion channel-linked receptors function in the simplest and direct way. These receptors are responsible for the rapid transmissions of signals across synapses in the nervous system. They transduce a chemical signals in the form of a pulse of neurotransmitter delivered to the outside of the target cell. When neurotransmitter binds, this type of receptor alters its conformation so as to open or close channel for the flow of specific types of ions (such as Na+, K+, Ca2) Ion-channel-linked Receptors Convert Chemical Signals Into Electrical Ones  Many Intracellular Signaling Proteins Act as Molecular Switches Signals received via G-protein-linked or enzyme-linked receptors are transmitted to elaborate relay systems formed from cascades of intracellular signaling molecules. Apart from a few small molecules like cyclic GMP, cyclic Loading… AMP, and Ca2+, these intracellular molecules are proteins. Some serves as chemical transducer and in response to one type of chemical signal they generate another. Others serve as messengers, receiving a signal in one part of the cell and moving to another to exert an affect Many intracellular signalling proteins act as molecular switches