Cell Signalling Pathway (intra and extra cellular signalling)
- 2. Cell Signaling Presented By: Aneela Rafiq, Biotechnology
- 3. General principle of cell communication • Prokaryotes and eukaryotes both communicate through signals. • Budding yeast: it secretes a peptide mating factor that signals cells of the opposite mating type to stop proliferating and prepare to mate. diploid cell which generating haploid cells with new assortments of genes
- 4. A) cells are normally spherical).B) in response to mating factor they put out a protrusion towards the source of mating
- 5. Extracellular Signal Molecules Bind to Specific Receptors • These include proteins, small peptides, amino acids, nucleotides, steroids, retinoid, fatty acid derivatives, and even dissolved gases such as nitric oxide and carbon monoxide. • Diffusion,exocytosis,displaying on extracellular membrane • Target cells respond by mean of proteins on their surface the “receptor”
- 7. Extracellular Signal Molecules Can Act Over Either Short or Long Distances • Contact dependent signaling • paracrine signaling: for short distance other wise it would be destroyed by neighboring target cells . • Synaptic cleft: between neurons of specialized organisms for far away target by axons nerve impulse is send that releases the neurotransmitters • Endocrine cell :that control the behavior of a cell here signaling molecules releases the hormones in blood stream, is relatively slow and is diluted
- 9. Autocrine Signaling Can Coordinate Decisions by Groups of Identical Cells • Development decision signals to cell of same type . • used to encourage groups of identical cells to make the same developmental decisions. • during which a group of identical cells can respond to a differentiation-inducing signal but a single isolated cell of the same type cannot. • cancer cells often use autocrine signaling
- 10. A group of identical cells produces a higher concentration of a secreted signal than does a single cell. When this signal binds back to a receptor on the same cell type, it encourages the cells to respond coordinately as a group
- 11. Gap Junctions • Gap Junctions Allow Signaling Information to Be Shared by Neighboring Cells • specialized cell-cell junctions • Ca2 + and cyclic AMP • electrically, with intracellular electrodes, or visually, after the microinjection of small water-soluble dyes
- 12. Each Cell Is Programmed to Respond to Specific Combinations of Extracellular Signal Molecules • Typical cell expose to different signals • signals can be soluble, bound to the extracellular matrix, or bound to the surface of a neighboring cell • deprived of these signals apoptosis
- 13. Different Cells Can Respond Differently to the Same Extracellular Signal Molecule • varies according to the set of receptor proteins the cell possesses • varies according to the intracellular machinery by which the cell integrates and interprets the signals it receives • , a single signal molecule often has different effects on different target cells. • Example: neurotransmitter acetylcholine stimulates the contraction of skeletal muscle cells decreases the rate and force of contraction in heart muscle cells
- 14. Nitric Oxide Gas Signals by Binding Directly to an Enzyme Inside the Target Cell • Extracellular signals hydrophilic molecules binds to the receptor Hydrophobic plasma membrane • Example : Regulate smooth muscle contraction Acetylcholine autonomic nerves walls of blood vessels cause relaxation of smooth muscles indirectly act on the endothelial cell release of NO mechanism of action of nitroglycerine angina nitroglycerine converted into no relaxation • Example in animals Carbon monoxide (CO) stimulating guanylyl cyclase across the target-cell plasma membrane regulate gene transcription
- 16. • Nuclear Receptors As Ligand-activated Gene Regulatory Proteins • The Three Largest Classes of Cell Surface Receptor Proteins • Most Activated Cell Surface Receptors spread Signals Through Small Molecules and a Network of Intracellular Signaling Proteins
- 17. Nuclear Receptors As Ligand-activated Gene Regulatory Proteins: • Diffusion and binding to intracellular receptor proteins by hydrophobic signal molecules. • Binding to receptor proteins Activation bind to DNA regulate transcription. • Receptors are structurally related
- 18. The hormones functioning as signaling molecules: • Steroid hormones, made of cholesterol. • Cortisol, in the cortex of the adrenal glands, effects metabolism. • steroid sex hormones. • Vitamin D, regulates Ca2+ metabolism, Ca2+ uptake in gut, reduce excretion in kidneys. • Thyroid hormones, amino acid tyrosine, ˂ metabolic rate. • These signal molecules are insoluble in water
- 19. The intracellular receptors for different hormones: • Receptors bind to DNA sequences adjacent to genes of ligands. • Transcriptional response; • Activation of a small number of specific genes primary response, protein activate other genes secondary response.
- 20. The Three Largest Classes of Cell Surface Receptor Proteins: • Water-soluble signal molecules bind to receptor proteins on surface of target cells. Ion channel linked receptors: e.g; active transport
- 21. 2. G protein linked receptors:
- 22. 3. Enzyme linked receptors:
- 23. Most Activated Cell Surface Receptors spread Signals Through Small Molecules and a Network of Intracellular Signaling Proteins: • Signals received, spread into cell interior by small and large Intracellular signaling molecules. • Small intracellular signaling molecules, second messengers. • Cyclic AMP and Ca2+, water-soluble, diffuse in the cytosol. • Diacylglycerol, lipid-soluble, diffuse in the plane of the cell membrane • large intracellular signaling molecules • Activate next signaling protein in chain or produce small intracellular mediators.
- 24. Classification of large intracellular signaling molecules: • Relay proteins • Messenger proteins • Adaptor proteins • Amplifier proteins • Transducer proteins • Bifurcation proteins • Integrator proteins
- 25. Other types of intracellular proteins: • Anchoring proteins • Scaffold proteins
- 26. Some Intracellular Signaling Proteins Act as Molecular Switches • Molecular switches • Another process switch off • Switching off is very important • Two classes
- 27. Classes of molecular switches 1. Phosphorylation 2. GTP-binding protein
- 28. Phosphorylation • Gain/lose phosphate group • Largest class; phosphorylation • Protein kinase/protein phosphatase • Phosphorylation cascade • Types of protein kinase • Distinct types of protein kinase
- 29. GTP-binding protein • Hydrolyze; GTP into GDP • Types of GTP-binding protein • Vesicular traffic • Others processes
- 31. Intracellular Signaling Complexes Enhance the Speed, Efficiency, and Specificity of the Response • G-protein-linked or enzyme-linked receptor • Activates multiple parallel signaling pathways • Influence multiple aspects
- 32. Two cases that the cell uses to achieve specificity 1. Scaffold proteins 2. Assembly of proteins
- 33. Scaffold proteins • Signaling complex • Unwanted cross talk • Freely diffusible
- 34. Assembly of proteins • Assemble around receptor • Cytoplasmic tail • Phosphorylated amino acids serve as docking sites • Modified phospholipid molecules
- 35. Two types of intracellular signaling complexes
- 36. Interactions Between Intracellular Signaling Proteins Are Mediated by Modular Binding Domains • Binding domains • Particular structural motif • Multiple combinations, like Lego bricks • New signaling pathways • Src homology 2 (SH2) domains and phosphotyrosine-binding (PTB) domains
- 37. A hypothetical signaling pathway using modular binding domains
- 38. Cells Can Respond Abruptly to a Gradually Increasing Concentration of an Extracellular Signal • Many responses to extracellular signal molecules, however, begin more shortly as the concentration of the molecule increases. (Ghosh & Greenberg, 1995). • Steroid hormone-induced responses (Ghosh & Greenberg, 1995). • All-or-none threshold responses (Ghosh & Greenberg, 1995).
- 39. A Cell Can Remember the Effect of Some Signals • After the signal has disappeared, the effect of an extracellular signal on a target cell can, in some cases, continue well. For example (Gotthardt et al., 2000) • Autophosphorylation (Gotthardt et al., 2000) • Turn on a series of muscle-specific gene regulatory proteins (Gotthardt et al., 2000)
- 40. Cells Can Adjust Their Sensitivity to a Signal • In responding to many types of stimuli, cells and organisms are able to detect the same percentage of change in a signal over a very wide range of stimulus intensities (Ahmad & Xiang, 2011).
- 41. Conclusion • Each cell respond to a specific set of extracellular signals produced by other cells. • These signals act in various combinations to regulate the behavior of the cell. • Ion-channel-linked receptors. • G-protein. • Enzyme-linked receptors • Cell can respond abruptly to a gradually increasing concentration of an extracellular signal • A Cell Can Remember the Effect of Some Signals • Cells Can Adjust Their Sensitivity to a Signal
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