Cell signaling Lec. 1 Dr. ali al-bayati - PowerPoint Presentation

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Cell signaling

Lec. 1

Dr. ali al-bayati

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IntroductionCell signaling: a biological mechanism that occurs in cells which gives cells an ability to receive or generate the signals in response to their surrounding environment.Cell to cell communication

between cells is mediated by extra-cellular signal molecules. Some of those operate over long distances. Others signal only to immediate neighboring cells.

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DefinitionsSignaling - Cell-cell communication or communication of the environment to the cells interior via signals.Signal transduction -

Process of converting extracellular signals into intra- cellular responses.

Ligand - The signaling molecule.Receptors -

Bind specific ligands. Transmit signals to intracellular targets. Different receptors can respond differently to the same ligand.

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Cell signaling can be classified based on the type of the signal. Mechanical signals are the forces exerted on the cell and the forces produced by the cell. These forces can both be sensed and responded by the cells.

Biochemical signals

are the biochemical molecules such as proteins, lipids, ions and gases. These signals can be categorized based on the distance between signaling and responder cells.

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Classification of signaling pathwayAutocrine Paracrine

Juxtacrine

Endocrine Synaptic

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The main difference between the different categories of signaling is the distance that the signal travels through the organism to reach the target cell.

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signals are produced by the target cell, are secreted, and affect the target cell itself via receptors. Sometimes autocrine cells can target cells close by if they are the same type of cell as the emitting cell.

Juxtacrine signaling occurs when the two type of cells are adjacent to each other

through protein molecules on the surface of the two cells.

Neurotransmitters represent an example.

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Cell signaling componentsSignaling moleculeReceptor

Signaling intermediate

Effector proteins

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Signaling molecules are the molecules that are responsible for transmitting information between cells in the body. The size, shape, and function of different types of signaling molecules can vary greatly. Some carry signals over short distances, while others transmit information over very long distances.

Types of signaling molecules

1) Hormone2) Neurotransmitter3) cytokines

Signaling molecules may trigger:

An immediate change in the metabolism of the cell (e.g., increased glycogenolysis when a liver cell detects adrenaline);

An immediate change in the electrical charge across the plasma membrane (e.g., the source of action potentials);

A change in the gene expression — transcription — within the nucleus. (These responses take more time).

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Types of Receptor:-Receptors can be divided into:-

Intracellular receptors.

Cell-surface receptors.

Ligand – gated ion channel receptors are a class of receptor that may occur both at the cell-surface or intracellular.

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Cell-surface receptors:-There are many different class of transmembrane receptor that recognizes different extracellular signaling molecules:-

G- protein – coupled receptors. e.g., chemokine receptors.

Receptor tyrosine Kinases. e.g., growth factor receptors.

Integrins.

Toll-like receptors.

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G-Protein – coupled Receptors.G protein-coupled receptor (GPCR), also called seven-transmembrane receptor or heptahelical receptor, protein located in the cell membrane that binds extracellular substances and transmits signals from these substances to an intracellular molecule called a G protein (guanine nucleotide-binding protein).

Some examples of GPCRs include beta-adrenergic receptors, which bind epinephrine; prostaglandin E2 receptors, which bind inflammatory substances called prostaglandins;

Structure; These receptors all have a similar structure with seven transmembrane domains. GPCRs associate with heterotrimeric G-proteins (green), that is, GTP-binding proteins composed of three different subunits: alpha, beta, and gamma. The subunits are tethered at the membrane surface by covalently attached lipid molecules.

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Activation; When a ligand binds, the receptor activates the attached G-protein by causing the exchange of GTP (yellow) for GDP (red). The activated G-protein then dissociates into an alpha (G-alpha) and a beta-gamma complex. G-alpha bound to GTP is active, and can diffuse along the membrane surface to activate (and sometimes inhibit) target proteins, often enzymes that generate second messengers. Likewise, the beta-gamma complex is also able to diffuse along the inner membrane surface and affect protein activity.

Inactivation

occurs because G-alpha has intrinsic GTPase activity. After GTP hydrolysis, G-alpha bound to GDP will reassociate with a beta-gamma complex to form an inactive G-protein that can again associate with a receptor.

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A specific example of a receptor that couples to this type of G-protein is the beta-1 adrenergic receptor found in the heart. Beta 1 receptors are the principal type of adrenergic receptor found in the heart. The ligand for this receptor is norepinephrine, the neurotransmitter that is released by sympathetic postganglionic neurons. (As well, the hormone epinephrine, released from the adrenal medulla, is also a ligand for these receptors.) Stimulation of beta-1 receptors causes increased cAMP and PKA activation. PKA phosphorylates various target proteins in cardiac cells to cause an increase in both the heart rate and the strength of cardiac muscle contraction. Beta-1 receptors are the targets of drugs (beta blockers) that are used to treat heart failure and hypertension.

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Receptor Tyrosine Kinases(RTK):-Receptor tyrosine kinases (RTKs) are transmembrane proteins; they are enzymes that that transfer phosphate groups from ATP to the amino acid Tyrosine on a protein. These cell surface receptors bind and respond to growth factors and other some hormones like insulin. RTKs play important roles in the regulation of cell growth, differentiation, and survival.

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Integrins:-Integrins are transmembrane receptors that mediate cell-adhesion. Integrins are produced by a wide variety of cell types, and play a role in the attachment of a cell to the extracellular matrix (ECM) and to other cells,

and in the signal transduction of signals received from extracellular matrix components such as fibronectin, collagen.

Important differences were between integrin signaling in circulating blood cells and that in non-circulating cells such as epithelial cells. Integrins at the cell-surface of circulating cells are inactive under normal physiological conditions.

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Toll like receptors (TLRs):-

TLRs are membrane glycoproteins, homology in the cytoplasmic receptors region-Interleukin-1 receptors (IL-1Rs) superfamily.

The extracellular region of TLRs contains leucine-rich repeat (LRR) motifs & IL1Rs contains three immunoglobulin-like domains

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They are a type of pattern recognition receptor and recognize molecules that are shared by pathogens but distinguishable from host molecules , once they have reached physical barriers such as the skin or intestinal tract mucosa and activate immune cell responses , they are play a key role in the innate immune system.

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Signal transduction It occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response. There are two stages in this process:

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. A signaling molecule activates a specific receptor protein on the cell membrane.2. A second messenger transmits the signal into the cell, eliciting a physiological

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Properties of cell signalingSpecificity Affinity

Cooperativity

SensitizationAmplification Integration

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Types of responses:-

Gene expression altered at the level

of transcription, RNA processing or translationEnzyme activities are altered Protein-protein interactions are induced

or inhibited

The

localization of certain proteins

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The Cell…– divides or stops dividing– differentiates– commits suicide or kills something– moves somewhere or stops moving

– alters its metabolism

– passes on the signal

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