Cells Signals - Lecture Notes

Cells signals Allotted Time : 40mint Number of slides :38 Assist. Prof. Dr. Nabeel Mohammed Naji AL-Sharafi 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 1 ...

Cells signals Allotted Time : 40mint Number of slides :38 Assist. Prof. Dr. Nabeel Mohammed Naji AL-Sharafi 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 1  General Objects  The vast majority of homeostatic systems require cell to cell communication via chemical messengers.  The first step in the action of any intercellular chemical messenger and the binding of the messenger to specific target-cell proteins 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 2  Contents 1. Signal transduction. 2. Signals. Receptors. Ligand Second messenger 3. Chemical messenger. 4. Receptor activation. 5. Intracellular Receptors(lipid-soluble Pathways). 6. Pathways Initiated by Plasma-Membrane Receptors. 7. Second mechanism in side the cells. 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 3  : signal transduction  Is the sequences of events by which the binding of a chemical messenger (hormone, neurotransmitter, or paracrine/autocrine agent) to a receptor causes the cell to respond to the messenger  is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellular response.  It also known as cell signaling in which the transmission of molecular signals from a cell's exterior to its interior. 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 4 Signals Biochemical received by cells must be transmitted effectively into the cell to ensure an appropriate response. This step is initiated by cell-surface receptors which triggers a biochemical chain of events inside the cell, and creating response Receptors. Proteins responsible for detecting stimuli Ligand signaling molecules that binds to receptors that trigger events inside the cell & they are primary messenger. As the result of binding the ligand to receptor, other molecules or second messengers are produced within the target cell. Second messengers relay the signal from one location to another (such as from plasma membrane to nucleus) leading to cascade of events/changes within a cell. 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 5 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 6  Chemical messenger 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 7  Receptor activation The combination of messenger with receptor causes a change in the conformation of the receptor. Receptor Response Changes activation s (1) the permeability, transport properties, or electrical state of the cell’s plasma membrane. (2) the cell’s metabolism. (3) the cell’s secretory activity. (4) the cell’s rate of proliferation and differentiation. (5) the cell’s contractile activity. 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 8 The important question is: How does receptor activation influence the cell’s internal proteins ? Signal transduction pathways differ at the very outset for : 1. Intracellular Receptors (lipid-soluble Pathways) 2. Plasma-membrane Receptors (lipid- insoluble messengers Pathways) 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 9  Intracellular Receptors (lipid-soluble.1 Pathways) steroid hormones, the thyroid hormones, and the steroid derivative, 1,25- dihydroxyvitamin D3. Structurally these hormones are all closely related 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 10 Two other points should be mentioned. -First, more than one gene may be subject to control by a single receptor type - second, in some cases the transcription of the gene(s) is decreased by the activated receptor rather than increased. 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 11  Pathways Initiated by Plasma-.2 Membrane Receptors  a- Receptors that themselves function as ion channels.  b. Receptors that themselves function as enzymes.  c. Receptors that are bound to and activate cytoplasmic JAK kinases.  d. Receptors that activate G proteins, which in turn act upon effector proteins—either ion channels or enzymes—in the plasma membrane. 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 12 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 13 1. First messengers. 2. Second messengers. 3. protein kinase. 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 14  a. Receptors That Function as Ion Channels activation of the receptor by a first messenger causes the channel to open. The opening results in an increase in the net diffusion across the plasma membrane of the ion or ions specific to the channel. change in the Electric Ion diffusion membrane signal potential cell’s response 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 15 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 16  b. Receptors That Function as Enzymes - The many receptors that possess intrinsic enzyme activity are all protein kinases. Of these, - Ex 1 : the great majority phosphorylate specifically the portions of proteins that contain the amino acid tyrosine; - they are termed tyrosine kinases. -The binding of a specific messenger to the receptor changes the conformation of the receptor so that its enzymatic portion, located on the cytoplasmic side of the plasma membrane, is activated. This results in autophosphorylation of the receptor 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 17 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 18 The are number of kinases : 1. Rapidly accelerated fibrosarcoma // Ser/Thr kinases (RAF) 2. Mitogen-activated protein kinase kinase (MAPKK) 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 19 Ex 2 : plasma-membrane receptors activity function as protein kinases. Receptor functions as a guanylyl cyclase - This signal transduction pathway is used by only a small number of messengers Guanylyl cyclase enzymes are present in the cytoplasm; in these cases, a first messenger—nitric oxide—diffuses into the cell and combines with the guanylyl cyclase there to trigger the formation of cGMP.) 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 20 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 21  C. Receptors that Interact with Cytoplasmic JAK Kinases separate cytoplasmic kinases, termed JAK kinases, which are bound to the receptor. (The term “JAK” has several derivations, including “just another kinase.”) In these cases, the receptor and its associated JAK kinase function as a unit; the binding of a first messenger to the receptor causes a conformational change in the receptor that leads to activation of the JAK kinase. 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 22  d. Receptors that Interact with G Proteins - largest, including hundreds of receptors. Bound to the receptor is a protein located on the inner surface of the plasma membrane and belonging to the family of proteins known as G proteins. -This change causes one of the three subunits of the G protein to link up with still another plasmamembrane protein, either an ion channel or an enzyme. These ion channels and enzymes are termed plasmamembrane effector proteins since they mediate the next steps in the sequences of events leading to the cell’s response. 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 23 The are two most important effector-protein enzymes 1. Adenylyl cyclase Cyclic AMP (cAMP) 2. phospholipase C- regulated by G proteins 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 24  1. Adenylyl Cyclase and Cyclic AMP (cAMP) 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 25 To take an actual example, one molecule of the hormone epinephrine can cause the generation and release by the liver of 108 molecules of glucose. 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 26  How can activation of a single molecule, cAMP dependent protein kinase, by cAMP be an event common to the great variety of biochemical sequences and cell responses initiated by cAMP-generating first messengers? The major answer is that cAMP-dependent protein kinase has a large number of distinct substrates it can phosphorylate a large number of different proteins 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 27 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 28  Phospholipase C, Diacylglycerol, and Inositol.2 Trisphosphate 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 29  Second mechanism in side the cells A- Calcium as a Second Messenger The calcium ion (Ca2) functions as a second messenger in a great variety of cellular responses to stimuli, both chemical (first messenger) and electrical. Common mechanisms by which stimulation of a cell leads to an increase in cytosolic Ca2 concentration: 1. Receptor activation a. Plasma-membrane calcium channels open in response to a first messenger; the receptor itself may contain the channel, or the receptor may activate a G protein that opens the channel via a second messenger. b. Calcium is released from the endoplasmic reticulum; this is mediated by second messengers, particularly IP3 and calcium entering from the extracellular fluid. c. Active calcium transport out of the cell is inhibited by a second messenger. 2. Opening of voltage-sensitive calcium channels 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 30 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 31  B. Receptors and Gene Transcription 1. The Receptors for lipid-soluble messengers, once activated by hormone binding, act in the nucleus as transcription factors to increase or decrease the rate of gene transcription. 2. Signal transduction pathways initiated by plasma-membrane receptors by phosphorylation, of these transcription factors. 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 32  (PRG ) 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 33  Cessation of Activity in Signal Transduction Pathways 1. Rapidly inactivated or broken down intracellularly example, cAMP by phosphodiesterase 2. Calcium is continuously being pumped out of the cell or back into the endoplasmic reticulum. 3. Decrease in the concentration of first messenger molecules in the region of the receptor by : a. The receptor becomes chemically altered (usually by phosphorylation), which lowers its affinity for a first messenger, and so the messenger is released; and b. Removal of plasma-membrane receptors occurs when the combination of first messenger and receptor is taken into the cell by endocytosis. 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 34  summary 1.Binding a chemical messenger activates a receptor, and this initiates one or more signal transduction pathways leading to the cell’s response. 2. Lipid-soluble messengers bind to receptors inside the target cell, and the activated receptor acts in the nucleus as a transcription factor to alter the rate of transcription of specific genes, resulting in a change in the concentration or secretion of the proteins coded by the genes. 3. Lipid-insoluble messengers bind to receptors on the plasma membrane. The pathways induced by activation of the receptor often involve second messengers and protein 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 35  - Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition 2001 -Guyton and Hall Textbook of Medical Physiology twelfth edition t , 2011 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 36  Estée Lauder 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 37  Thanks for Attentions 11/06/2024 04:54 PM Dr. Nabeel AL-Sharafi Cells signals 38