BIO 467/567 Signal Transduction Course 0: Kickoff Ozgur Kutuk, MD, PhD Molecular Biology, Genetics and Bioengineering Program
Textbook: Cell Signalling, Fourth Edition, John T. Hancock, 2017, ISBN: 9780199658480
Learning Objectives Introduction to Cell Communication Cell Signaling Pathways
Who Communicates? Why? Unicellular organisms To sense environment Is there enough food/light? Are there toxins in the vicinity? Cells in multicellular organisms To function cooperatively with neighboring and distant cells of the organism Normal cells + mating factor
Types of Cell Communication-1 Autocrine Regulate self or group of similar cells e.g., Signaling of some interleukins e.g. IL-6 Growth signaling in many types of cancer cells Gap Junctions Direct contact between adjacent cell cytoplasm Transport of ions and small molecules between cells (e.g., between adjacent neurons) Paracrine Signal induces changes in neighboring cells e.g., Signaling by Fibroblast growth factors
Types of Cell Communication-2 Endocrine Secretion of hormones - directly into blood for transport to target cells Action seen in target cells far from the source Action is prolonged Insulin - secreted by pancreas, acts on liver, muscle, and fat cells Exocrine Secretion of enzymes and/or other fluids e.g., sweat, saliva via specific ducts Action close to site of secretion Activity short-term Pancreatic digestive enzymes - trypsin, chymotrypsin, elastase , carboxypeptidase , lipase, amylase
Properties of Cell Signals Cells are programmed to respond to signals (and combinations of signals) in specific ways Different cells may respond to the same signal in different ways
Step 1: Reception Receptor specifically binds signal molecule (sometimes called ligand) Cell surface receptors Embedded in plasma membrane Bind water-soluble ligands Intracellular receptors Present in cytoplasm or nucleus Binds small and hydrophobic ligands (that can pass through the cell membrane)
Step 2: Signal Transduction Relay signals from receptors to target(s) Second messenger: small molecules in cytoplasm Messenger molecules: proteins relaying message Many are molecular switches – turn on and off Types of messenger protein: Relay protein or messenger Adaptor proteins Amplifier Transducer Integrator
Step 3: Response Regulation of cytoplasmic activities Rearrangement of cytoskeleton Movement of vesicles to cell surface Release of stored hormones, messengers etc. Translocate specific receptors/channels to cell surface Activation or inhibition of enzyme(s) Regulation of nuclear activities Gene regulation – activation or inhibition Transcription cell proliferation/differentiation
Feedback Regulation All cell signals must be attenuated Feedback mechanisms at all the steps may regulate the response Surface receptors may be internalized Signal transducers may be removed/modified e.g., Ca 2+ ions sequestered or PO 4 proteins de-PO 4 Response may produce new proteins that block signaling