A report on Signal transduction

Simplified representation of major signal transduction pathways in mammals.
Domino cascade is a daily life analogy of signal transduction cascade
3D Medical animation still showing signal transduction.
An overview of integrin-mediated signal transduction, adapted from Hehlgens et al. (2007).
How to read signal transduction diagrams, what does normal arrow and flathead arrow means.
Elements of Signal transduction cascade networking
Occurrence of the term "signal transduction" in MEDLINE-indexed papers since 1977

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.

- Signal transduction
Simplified representation of major signal transduction pathways in mammals.

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Overall

General Schematic of Second Messenger Mechanism

Second messenger system

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Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers.

Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers.

General Schematic of Second Messenger Mechanism
The phosphoinositol signaling pathway

They are one of the triggers of intracellular signal transduction cascades.

Different types of extracellular signaling

Cell signaling

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Ability of a cell to receive, process, and transmit signals with its environment and with itself.

Ability of a cell to receive, process, and transmit signals with its environment and with itself.

Different types of extracellular signaling
Differences between autocrine and paracrine signaling
Figure 2. Notch-mediated juxtacrine signal between adjacent cells.
Transmembrane receptor working principle
The AMPA receptor bound to a glutamate antagonist showing the amino terminal, ligand binding, and transmembrane domain, PDB 3KG2
A G Protein-coupled receptor within the plasma membrane.
VEGF receptors are a type of enzyme-coupled receptors, specifically tyrosine kinase receptors
Figure 3. Key components of a signal transduction pathway (MAPK/ERK pathway shown)
Signal transduction pathways that lead to a cellular response

Signal transduction begins with the transformation (or transduction) of a signal into a chemical one, which can directly activate an ion channel (ligand-gated ion channel) or initiate a second messenger system cascade that propagates the signal through the cell.

General scheme of kinase function

Protein kinase

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Kinase which selectively modifies other proteins by covalently adding phosphates to them as opposed to kinases which modify lipids, carbohydrates, or other molecules.

Kinase which selectively modifies other proteins by covalently adding phosphates to them as opposed to kinases which modify lipids, carbohydrates, or other molecules.

General scheme of kinase function
Above is a ball-and-stick model of the inorganic phosphate molecule (HundefinedPO42−). Colour coding: P (orange); O (red); H (white).
Calcium/calmodulin-dependent protein kinase II (CaMKII) is an example of a serine/threonine-specific protein kinase.

Up to 30% of all human proteins may be modified by kinase activity, and kinases are known to regulate the majority of cellular pathways, especially those involved in signal transduction.

The seven-transmembrane α-helix structure of a G-protein-coupled receptor

Cell surface receptor

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Cell surface receptors (membrane receptors, transmembrane receptors) are receptors that are embedded in the plasma membrane of cells.

Cell surface receptors (membrane receptors, transmembrane receptors) are receptors that are embedded in the plasma membrane of cells.

The seven-transmembrane α-helix structure of a G-protein-coupled receptor
= extracellular space = plasma membrane = intracellular space
External reactions and internal reactions for signal transduction (click to enlarge)
Three conformation states of acetylcholine receptor (click to enlarge)
Sketch of an enzyme-linked receptor structure (structure of IGF-1R) (click to enlarge)
Flow charts of two strategies of structure-based drug design

In the process of signal transduction, ligand binding affects a cascading chemical change through the cell membrane.

crystal structure of the filamin a repeat 21 complexed with the integrin beta7 cytoplasmic tail peptide

Integrin

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Integrins are transmembrane receptors that facilitate cell-cell and cell-extracellular matrix (ECM) adhesion.

Integrins are transmembrane receptors that facilitate cell-cell and cell-extracellular matrix (ECM) adhesion.

crystal structure of the filamin a repeat 21 complexed with the integrin beta7 cytoplasmic tail peptide
Integrins are localised at the growth cone of regenerating neurons.

Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, organization of the intracellular cytoskeleton, and movement of new receptors to the cell membrane.

cAMP represented in three ways

Cyclic adenosine monophosphate

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Second messenger important in many biological processes.

Second messenger important in many biological processes.

cAMP represented in three ways
Adenosine triphosphate

cAMP is a derivative of adenosine triphosphate (ATP) and used for intracellular signal transduction in many different organisms, conveying the cAMP-dependent pathway.

The leukocyte adhesion cascade steps and the key molecules involved in each step

Biochemical cascade

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Series of chemical reactions that occur within a biological cell when initiated by a stimulus.

Series of chemical reactions that occur within a biological cell when initiated by a stimulus.

The leukocyte adhesion cascade steps and the key molecules involved in each step

This stimulus, known as a first messenger, acts on a receptor that is transduced to the cell interior through second messengers which amplify the signal and transfer it to effector molecules, causing the cell to respond to the initial stimulus.

Schematic of cell adhesion

Cell adhesion

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Process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface.

Process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface.

Schematic of cell adhesion
Overview diagram of different types of cell junctions present in epithelial cells, including cell–cell junctions and cell–matrix junctions.
Adheren junction showing homophilic binding between cadherins and how catenin links it to actin filaments
Gap junctions showing connexons and connexins
Hemidesmosomes diagram showing interaction between integrins and laminin, including how integrins are linked to keratin intermediate filaments

Cell adhesion links cells in different ways and can be involved in signal transduction for cells to detect and respond to changes in the surroundings.

IP3 anion with oxygen atoms (red) and the hydrogen atoms involved in docking to InsP3R (dark blue) indicated

Inositol trisphosphate

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Inositol phosphate signaling molecule.

Inositol phosphate signaling molecule.

IP3 anion with oxygen atoms (red) and the hydrogen atoms involved in docking to InsP3R (dark blue) indicated
PLC cleavage of PIP2 to IP3 and DAG initiates intracellular calcium release and PKC activation.

Together with diacylglycerol (DAG), IP3 is a second messenger molecule used in signal transduction in biological cells.

Post-translational modification of insulin. At the top, the ribosome translates a mRNA sequence into a protein, insulin, and passes the protein through the endoplasmic reticulum, where it is cut, folded, and held in shape by disulfide (-S-S-) bonds. Then the protein passes through the golgi apparatus, where it is packaged into a vesicle. In the vesicle, more parts are cut off, and it turns into mature insulin.

Post-translational modification

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Post-translational modification (PTM) refers to the covalent and generally enzymatic modification of proteins following protein biosynthesis.

Post-translational modification (PTM) refers to the covalent and generally enzymatic modification of proteins following protein biosynthesis.

Post-translational modification of insulin. At the top, the ribosome translates a mRNA sequence into a protein, insulin, and passes the protein through the endoplasmic reticulum, where it is cut, folded, and held in shape by disulfide (-S-S-) bonds. Then the protein passes through the golgi apparatus, where it is packaged into a vesicle. In the vesicle, more parts are cut off, and it turns into mature insulin.
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PTMs are important components in cell signaling, as for example when prohormones are converted to hormones.