CELL SIGNALING (BIO-203)

1. CELL SIGNALING (BIO-203) Credit Hrs 3

2. Course Contents • Overview of cell signaling • Principles of cell signaling • Types of ligands and receptors • Signaling through enzyme liked cell-surface receptors • Receptor tyrosine kinases and non-receptor tyrosine kinases • Signaling via receptor tyrosine kinases • Signaling via tyrosine kinase associated receptors • Signaling via receptor serine-/threoninekinases • Signaling through G protein linked receptors • Small GTPases • G protein coupled receptors • Lipid (2nd messengers)-mediated cell signaling • Synaptic signaling • ATP-signaling • Purinergic (P2X and P2Y) signaling • iNOSsiganling • Cell adhesion molecules • Signaling events in acute inflammation (native immunity) • Events at the postcapillaryvenule • Wound repair • Hematopoiesis • Why and how do cancer cells become independent of extracellular signals? • Selected examples • Plant cell signaling (role of growth factors, hormones and pheromones) • Plant defense mechanism • Signaling in microbes

3. Recommended Books • Molecular Cell Biology by Lodish and co. 6th Ed • Molecular Biology of the Cell by Bruce Albert and Dennis Bray. Garland Publishing Inc, New York and London. • Handbook of Cell SignalingVol 1-3, by Ralph Bradshaw, and Edward Dennis. • Cell Signalling, by John T. Hancock, 2nd ed. Oxford University Press. • Apoptosis, Cell Signaling, and Human Diseases: Molecular Mechanisms, Volume 2by RakeshSrivastava. • Cell Signaling and Growth Factors in Development: From Molecules to Organogenesis by Klaus Unsicker (Editor), Kerstin Krieglstein. • Signal Transduction by Bastien D. Gomperts. • The Biochemistry of Cell Signallingby Ernst J. M. Helmreich.

4. Total Marks • First OHT 15 marks • Second OHT 15 marks • Final Exam 50 mark • Quizzes (2-4)10 marks • Assignment/project /presentation10 marks

5. Time table • Wed (11:30-1:00) • Thurs (11:30-1:00)

6. Cell Signaling (Lecture 1)

7. Introduction • Cells can not live in an isolated environment. • Prokaryotes communicate with each other, other organisms and surrounding environment. • Eukaryotes e.g yeasts, slime molds, and protozoans mate, differentiate and respond to the environment by secreting pheromones • Cells are able to receive and process signals. • Individual cells receive many signals simultaneously, and they then integrate the information they receive into a unified action plan. • They also send out messages to other cells both near and far.

8. What kind of signals do cells receive? • Most cell signals are chemical in nature. • Prokaryotic organisms have sensors that detect nutrients and help them navigate toward food sources. • In multicellular organisms, growth factors, hormones, neurotransmitters, and extracellular matrix components are some of the many types of chemical signals cells use. • These substances can exert their effects locally, or they might travel over long distances. • Some cells also respond to mechanical stimuli. For example sensory cells in skin and ear.

9. Types of signaling molecules • Small molecules: amino acids, lipid derivatives, acetylcholine • Peptides: ACTH, vasopressin • Soluble proteins: Insulin, growth hormones

10. Signaling in plants and animals • In plants and animals, extra cellular signaling molecules control • Metabolism • Growth and differentiation of tissues • Synthesis and secretion of proteins • Composition of intracellular and extracellular fluids

11. General principle signaling • Synthesis of signaling molecules by the signaling cells • Release of signaling molecules • Transport of the signal to the target cell • Detection of a signal by a specific receptor protein present on the target cell • A change in cellular metabolism, function or development triggered by the receptor-signal complex • Removal of the signal, which often terminate the cellular response

12. 1 3 2 Signaling cell 4 5 6

13. Cellular responses due to cell signaling • Changes in the activity or function of specific enzymes and other proteins present in the cells • Changes in the amount of protein produced by a cell e.g. modification of transcription factors that stimulate or repress gene expression

14. Types of signaling

15. Autocrine Signaling Can Coordinate Decisions by Groups of Identical Cells • Cells send signals to other cells. • Cells send signals to themselves. • Cell secretes signaling molecules that can bind back to its own receptors. • It is most effective when carried out simultaneously by neighboring cells of the same type. Thus autocrine signaling is thought to be one possible mechanism underlying the "community effect" observed in early development, where a group of identical cells can respond to a differentiation-inducing signal but a single isolated cell of the same type cannot.

16. (a) (b) (c) (d) (c1) (c2) (c3) (c4) (c5) (c6) (c7) (c8) (c9) (c10) Gap Junctions Allow Signaling Information to Be Shared by Neighboring Cells • Signals are passed to the neighboring cells through gap junctions. • These are specialized cell-cell junctions that can form between closely apposed plasma membranes, directly connecting the cytoplasms of the joined cells via narrow water-filled channels.

17. The channels allow the exchange of small intracellular signaling molecules, such as Ca2+ and cyclic AMP, but not of macromolecules, such as proteins or nucleic acids. • Thus cells connected by gap junctions can communicate with each other directly without having to deal with the barrier presented by the intervening plasma membranes. • gap-junction communication helps adjacent cells of a similar type to coordinate their behavior. • It is not known, however, which particular small molecules are important as carriers of signals through gap junctions; nor has the precise function of gap-junction communication in animal development been defined.

18. Receptor protein exhibit ligand binding effect • Receptor present on Plasma or nuclear membrane has ligand binding sites • Signaling molecules (hormones, pheromones or neurotransmitters) act as ligands • Confirmational change occurs in the receptor that initiate a sequence of chemical reactions • Receptor proteins are specific for each horomone

19. Different cells have different sets of receptor for the same ligand and each of which induces a different response • Different cells respond in a variety of way to the same ligand (e.g. acetylcholine) • Different ligands can induce the same cellular response in some cells (glucagon/epinephrine) • In most receptor-ligand system, the ligand do not have any function except to bind to receptor • Upon binding it changes the properties of receptor which then produce signals to the cell that a specific product is present • Target cells often degrade or modify the ligand to terminate or modify their response

20. Those who know Light in the world are those, who know Guides of mankind are those, who know When looking for the road to God And Prophet, ask from those, who know The alchemist in his research Finds sympathy from those, who know A desert stone will turn to gold In company with those, who know Those are not humans, only shells The empty ones, who do not know (Rehman Baba)

21. Believe in yourself • “Don't be satisfied with stories, how things have gone with others. Unfold your own myth.”  Rumi • “Life is too short to waste any amount of time on wondering what other people think about you. In the first place, if they had better things going on in their lives, they wouldn't have the time to sit around and talk about you. What's important to me is not others' opinions of me, but what's important to me is my opinion of myself.”  Anonymous