بسم الله الرحمن الرحيم

1. بسم الله الرحمن الرحيم

2. Cell Signaling

3. Cell signaling Plant cells respond to growth hormones and to variations in sunlight. Animal cells exchange information about e.g. the concentrations of ions and glucose in extracellular fluids

4. The signal represents information that is detected by specificreceptorsand converted to a cellularresponse, which always involves a chemicalprocess. • This conversion of information into a chemical change,(signal transduction ), is a universal property of living cells. Response (chemical change) Change to information signal transduction

5. one cell sends a signal molecule (ligand) • and other cell has a molecule responsible for reading an information (receptor) • and is able to conduct a special reaction in answer to the signal. Primary Messenger Feed-back Regulation Second Messenger N.B. signal molecule = ligand

6. c c c c

7. A cell targeted by a particular chemical signal has a receptor protein that recognizes the signal molecule.

10. Effects of the siganling: • change of shape or movement, • changes in gene expression, Combination of many signals may be responsible for: • survival, • division, • differentiation, • death of the cell.

11. The receptorsbind the signal molecule, amplify the signal, integrate it with input from other receptors, and transmit it into the cell. • If the signal persists,   receptor desensitization   reduces or ends the response.

12. 4 Features Of Signal Transducing Systems • Specificity • Amplification • Desensitization • Integration

17. Types of Cell Signaling A. Direct Signaling • Signal passes from cell to cell withoutentering extracellular medium e.g. through Gap junctions – specialized protein complexes that create an aqueous pore between two adjacent cells • This allows Hydrophilic chemical messengers to travel across the hydrophobic lipid membrane • Signaling molecules are often ions

18. B. Indirect Signaling: 3 steps • Releasesa chemical messenger by signaling cell • Transport :  messenger travels through extracellularmediumto the target cell • Communication : the signal bindsto a receptor on the target cell& activatesa signal transduction pathway in target cell

19. Types (Modes) of Cell Signaling • Direct Signaling (through gap junctions) • Autocrine signaling (Self-affection) • Paracrine signaling (on surrounding cells) • Endocrine signaling (on cells far away) • ( Nerve signaling )

20. Types (Systems) for Cell Signaling

21. Types of signaling molecules • Substances which can penetrate plasma membrane (hydrophobicsignaling molecules) • And activate the enzyme pathways, • And react with intracellular receptors e.g.STEROIDS THYROID HORMONES • Substances which have receptors in the plasma membrane.( hydrophilic signaling molecules) e.g. Insulin & Glucagon

22. Types of signaling molecules

23. TYPES OF RECEPTORS Membrane receptors: Ion channels, Coupled with G protein, Coupled with an enzyme. • MEMBRANE RECEPTORS • IONCHANNEL-LINKED • G-PROTEIN-LINKED • ENZYME-LINKED • -CYTOPLASMIC AND NUCLEARRECEPTORS

24. Primary messengers • Hormones, • Growth factors  IGF, EGF, NGF, • Neurotransmitters – dopamine, Ach, • Lymphockines – Interleukins, • Drugs.

25. Second (2nd) messengers • Ions - Ca 2+ • IP3, diacyloglicerol, • cAMP, • cGMP

26. Eukaryotic cells have six general types of signaling mechanisms: • Gated ion channels; • Receptorenzymes; • Membrane proteins that act through G proteins • Nuclearproteins (receptors) that bind steroids and act as transcription factors; • Membraneproteinsthat attract and activate soluble protein kinases; and • Adhesion receptors that carry information between the extracellular matrix and the cytoskeleton.

28. Cyclic AMP • The nucleotide cAMP(adenosine 3`,5`-cyclic monophosphate) is synthesized by membrane-bound adenylatecyclaseson the inside of the plasma membrane. • The adenylatecyclases cyclize ATP to cAMP by cleaving diphosphatePPi). • The degradation of cAMP to AMP is catalyzed by phosphodiesterases

30. Adenylatecyclase activity is regulated by G proteins (Gs and Gi), which in turn are controlled by extracellular signals via G proteins-coupled receptors. • c AMP activates Protein Kinase A (cAMP Dependent Protein Kinase) catalyzes transfer of phosphate from ATP to serine or threonine residues of various cellular proteins, altering their activity. • cGMPalso acts as a second messenger. • It is involved in Vision and in the signal transduction of NO (Nitric Oxide)

31. Adrenaline & Glucagoneincrease cAMPlevel because they stimulate Adenylatecyclase + Insulin reduces the cAMP level because it activates the phosphodiesterases --

32. Calcium • Calcium is a signaling substance. • The concentrationof Ca2+ ions in cytoplasm is normally very low, as it is kept down by ATP-driven Ca2+ pumps and Na+/Ca2+ exchangers. • Specific signals (e. g., an action potential or second messenger such as InsP3 or cAMP) can trigger a sudden increase in the cytoplasmic Ca2+ level by opening Ca2+ channels in the plasma membrane or in the endoplasmic (sarcoplasmic) reticulum membranes

33. The biochemical effects of Ca2+ in the cytoplasmaremediated by special Ca2+-binding proteins (“calcium sensors”), Including annexins, calmodulin, and troponin C in muscle. • Ca2+ - calmodulinComlex interact with other proteins and modulates their properties. • By this mechanism, Ca2+ ions regulate the activity of enzymes, ion pumps, and components of the cytoskeleton.

34. Inositol 1,4,5-trisphosphate (IP3)and diacylglycerol(DAG) • Type Gq(G proteins) activate phospholipase C. • This enzyme creates two second messengers from the membrane phospholipid phosphatidylinositol bisphosphate(PInsP2), • Inositol Triphosphate (IP3) migrates to the endoplasmic reticulum (ER), where it opens Ca2+ channels that allow Ca2+ to flow into the cytoplasm. • By contrast, Diacyl-glycerol (DAG), which is lipophilic, remains in the membrane, where it activates type C protein kinases, which phosphorylate proteins in the presence of Ca2+ ions and thereby pass the signal on.

36. References • Lehninger PRINCIPLES OF BIOCHEMISTRY - Fourth Edition • Color Atlas of Biochemistry - Second edition, - 2005