Cellular Signalling - Notes

Cellular Signalling local signaling The Three Stages of Cell Signaling : 1-Signal Reception 2- Signal Transduction 3- Cellular Response G protein-coupled receptors ( GPCRs ) Receptor tyrosine kinases ( RTKs ) Ion channel receptors Intracellular Receptors Protein Phosphorylation and Dephosphorylation Protein kinases Protein phosphatases Small Molecules and Ions as Second Messengers Nuclear and Cytoplasmic Responses signaling molecule binds to a receptor protein, causing it to change shape Cascades of molecular interactions transmit signals from receptors to relay molecules in the cell 1- Cyclic AMP (cAMP) Adenylyl cyclase Cells in a multicellular organism communicate via signaling molecules cell junctions cell-surface molecules Synaptic signaling paracrine signaling The binding between a signal molecule (ligand) and receptor is highly specific A shape change in a receptor is generally the initial transduction of the signal Most signal receptors are plasma membrane proteins, but others are located inside the cell G protein-coupled receptors (GPCRs) are cell-surface transmembrane receptors that work with the help of a G protein G proteins bind the energy-rich GTP The G protein acts as an on/off switch: If GDP is bound to the G protein, the G protein is inactive Receptor tyrosine kinases (RTKs) are membrane receptors that catalyze the transfer of phosphate groups from ATP to another protein A receptor tyrosine kinase can trigger multiple signal transduction pathways at once Abnormal functioning of RTKs is associated with many types of cancers A ligand-gated ion channel receptor acts as a gate that opens and closes when the receptor changes shape When a signal molecule binds as a ligand to the receptor, the gate allows specific ions, such as Na or Ca Intracellular receptor proteins are found in the cytoplasm or nucleus of target cells Small or hydrophobic chemical messengers can readily cross the membrane and activate receptors Examples of hydrophobic messengers are the steroid and thyroid hormones of animals An activated hormone-receptor complex can act as a transcription factor, turning on or off specific genes The binding of a signaling molecule to a receptor triggers the first step in a chain of molecular interactions The activated receptor activates another protein, which activates another, and so on, until the protein producing the response is activated At each step, the signal is transduced into a different form, commonly a shape change in a protein Phosphorylation and dephosphorylation of proteins are commonly used in cells to regulate protein activity Protein kinases transfer phosphates from ATP to protein, a process called phosphorylation Many relay molecules in signal transduction pathways are protein kinases, creating a phosphorylation cascade Protein phosphatases rapidly remove the phosphates from proteins, a process called dephosphorylation This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off, or up or down, as required a signal transduction pathway leads to regulation of one or more cellular activities The response may occur in the nucleus or in the cytoplasm Many signaling pathways regulate the synthesis of enzymes or proteins, usually by turning genes on or off in the nucleus The final activated molecule in the signaling pathway may function as a transcription factor* transcription factor: is any protein that binds to DNA and controls gene expression Other pathways may regulate the activity of proteins rather than their synthesis (a cytoplasmic response) Inactivation mechanisms are an essential aspect of cell signaling When signal molecules leave the receptor,the receptor reverts to its inactive state and therefore the signal is terminated (switched off) 2- Calcium Ions and Inositol Triphosphate ( IP ) Animal and plant cells have cell junctions that directly connect the cytoplasm of adjacent cells Signaling substances in the cytosol can pass between adjacent cells Local signaling is especially important in embryonic development, immune response, and maintaining adult stem cell populations animal cells communicate using secreted messenger molecules that travel only short distances Growth factors , which stimulate near by target cells to grow and divide, are one class of such local regulators in animals Synaptic signaling occurs in the animal nervous system when a neurotransmitter is released in response to an electric signal long-distance signaling In long-distance signaling, plants and animals use molecules called hormones The ability of a cell to respond to a signal depends on whether or not it has a receptor specific to that signal In hormonal (orendocrine) signaling in animals specialized cells release hormones, which travel to target cells via the circulatory system direct contact using secreted messenger Animal cells may also communicate by direct contact between cell-surface molecules 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 ) a small molecule produced from ATP, and one of the most widely used second messengers an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal cAMP usually activates protein kinase A,which phosphorylates various other proteins Calcium ions ( Ca ) act as a second messenger in many pathways Calcium is an important second messenger because cells can regulate its concentration 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 ) and diacylglycerol ( DAG ) as additional second messengers main types of membrane receptors phosphorylation dephosphorylation P from ATP to protein Remove P from protein Many signal molecules trigger formation of cAMP Other components of cAMP pathways are G proteins, G protein-coupled receptors, and protein kinases