Signal transduction

Signal transduction 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. The changes elicited by ligand binding (or signal sensing) in a receptor give rise to a biochemical cascade, which is a chain of biochemical events as a signaling pathway.

A biochemical cascade, also known as a signaling cascade or signaling pathway, is a series of chemical reactions which are initiated by a stimulus (first messenger) acting on a receptor that is transduced to the cell interior through second messengers (which amplify the initial signal) and ultimately to effector molecules, resulting in a cell response to the initial stimulus.

Signal transduction 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.

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 changes elicited by ligand binding (or signal sensing) in a receptor give rise to a biochemical cascade, which is a chain of biochemical events as a signaling pathway.

Systems biology studies the underlying structure of cell-signaling networks and how changes in these networks may affect the transmission and flow of information (signal transduction).

Such effectors are often linked to second messengers, which can activate secondary effectors, and so on. Some of them create second messengers such as cyclic AMP and IP 3, the latter controlling the release of intracellular calcium stores into the cytoplasm.

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

Most ligands are soluble molecules from the extracellular medium which bind to cell surface receptors.

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

The prevalence of basement membranes in the tissues of Eumetazoans means that most cell types require attachment to survive.

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.

Components of the extracellular matrix such as fibronectin and hyaluronan can also bind to such receptors (integrins and CD44, respectively). Such signaling is mainly orchestrated in focal adhesions, regions where the integrin-bound actin cytoskeleton detects changes and transmits them downstream through YAP1.

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.

Such signaling is mainly orchestrated in focal adhesions, regions where the integrin-bound actin cytoskeleton detects changes and transmits them downstream through YAP1.

A cell's ability to dynamically form microfilaments provides the scaffolding that allows it to rapidly remodel itself in response to its environment or to the organism's internal signals, for example, to increase cell membrane absorption or increase cell adhesion in order to form cell tissue.

Signal transduction 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.

This is the mechanism in many forms of signal transduction, for example the way in which incoming light is processed in the light-sensitive cells of the retina.

These are transmitted from neuron to neuron in a process called synaptic transmission.

The binding of neurotransmitters to receptors in the postsynaptic neuron can trigger either short term changes, such as changes in the membrane potential called postsynaptic potentials, or longer term changes by the activation of signaling cascades.

The nature of such stimuli can vary widely, ranging from extracellular cues, such as the presence of EGF, to intracellular events, such as the DNA damage resulting from replicative telomere attrition.

The tyrosine kinase activity, in turn, initiates a signal transduction cascade that results in a variety of biochemical changes within the cell – a rise in intracellular calcium levels, increased glycolysis and protein synthesis, and increases in the expression of certain genes including the gene for EGFR – that ultimately lead to DNA synthesis and cell proliferation.

These molecular events are the basic mechanisms controlling cell growth, proliferation, metabolism and many other processes.

Some of the key proteins are important for cell adhesion between myocytes and some are involved in adhesion-dependent cell-to-cell signal transduction that allows for a cascade of cell fusion events.

In multicellular organisms, signal transduction pathways have evolved to regulate cell communication in a wide variety of ways.

In eukaryotic cells, most intracellular proteins activated by a ligand/receptor interaction possess an enzymatic activity; examples include tyrosine kinase and phosphatases.

Phosphorylation of proteins by kinases is an important mechanism in communicating signals within a cell (signal transduction) and regulating cellular activity, such as cell division.

Other activated proteins interact with adaptor proteins that facilitate signaling protein interactions and coordination of signaling complexes necessary to respond to a particular stimulus.

Signal transducing adaptor proteins (STAPs) are proteins that are accessory to main proteins in a signal transduction pathway.

For example, calcium ions bind to the EF hand domains of calmodulin, allowing it to bind and activate calmodulin-dependent kinase.

Once bound to Ca 2+, calmodulin acts as part of a calcium signal transduction pathway by modifying its interactions with various target proteins such as kinases or phosphatases.

PIP 3 and other phosphoinositides do the same thing to the Pleckstrin homology domains of proteins such as the kinase protein AKT.

Through these interactions, PH domains play a role in recruiting proteins to different membranes, thus targeting them to appropriate cellular compartments or enabling them to interact with other components of the signal transduction pathways.

Some of them create second messengers such as cyclic AMP and IP 3, the latter controlling the release of intracellular calcium stores into the cytoplasm.

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

In mammals, light controls the sense of sight and the circadian clock by activating light-sensitive proteins in photoreceptor cells in the eye's retina.

The function of the photoreceptor cell is to convert the light energy of the photon into a form of energy communicable to the nervous system and readily usable to the organism: This conversion is called signal transduction.

The interaction between the cytoplasmic domains stimulates the autophosphorylation of tyrosine residues within the intracellular kinase domains of the RTKs, causing conformational changes.

It occurs in proteins that are part of signal transduction processes and functions as a receiver of phosphate groups that are transferred by way of protein kinases.

Histidine-specific protein kinases are structurally distinct from other protein kinases and are found in prokaryotes, fungi, and plants as part of a two-component signal transduction mechanism: a phosphate group from ATP is first added to a histidine residue within the kinase, then transferred to an aspartate residue on a receiver domain on a different protein or the kinase itself, thus activating the aspartate residue.

Histidine kinases (HK) are multifunctional, and in non-animal kingdoms, typically transmembrane, proteins of the transferase class of enzymes that play a role in signal transduction across the cellular membrane.

Receptor tyrosine kinases (RTKs) are transmembrane proteins with an intracellular kinase domain and an extracellular domain that binds ligands; examples include growth factor receptors such as the insulin receptor.

Kinases are used extensively to transmit signals and regulate complex processes in cells.

The typical ligands for nuclear receptors are non-polar hormones like the steroid hormones testosterone and progesterone and derivatives of vitamins A and D. To initiate signal transduction, the ligand must pass through the plasma membrane by passive diffusion.

Steroids have two principal biological functions: as important components of cell membranes which alter membrane fluidity; and as signaling molecules.

In the case of the circadian clock, a different photopigment, melanopsin, is responsible for detecting light in intrinsically photosensitive retinal ganglion cells.

It resembles invertebrate opsins far more than vertebrate photopigments, especially in its amino acid sequence and downstream signaling cascade.

Integrins lack kinase activity; hence, integrin-mediated signal transduction is achieved through a variety of intracellular protein kinases and adaptor molecules, the main coordinator being integrin-linked kinase.

Integrin-linked kinase is an enzyme that in humans is encoded by the ILK gene involved with integrin-mediated signal transduction.