As a signal transduction and signal conversion , signal transmission or signal transmission in the are Biochemistry and Physiology processes referred to, by means of which cells , for example, to external stimuli react, convert them to forward as a signal into the cell and run through a signal chain to the cellular effect. A large number of enzymes and secondary messenger substances ( second messengers ) are often involved in these processes , on one level or on several successive levels (signal cascade). Under certain circumstances, the original signal can be significantly amplified (signal amplification). Signals from different signaling pathways are often related and integrated through "crosstalk" in the cytoplasm or in the cell nucleus . The entirety of all signal paths in a cell type is also referred to as its signal network . Signal networks are plastic and vary e.g. B. in different stages of development of an organism .
Signal transduction processes are of essential importance for unicellular organisms in order to be able to react to changes in their environment, for example by regulating metabolism and gene expression , and to ensure survival. In multicellular organisms , cellular signal transduction is also an important step in the processing of signals that are communicated via extracellular messenger substances such as hormones and neurotransmitters , as well as for the absorption of internal (e.g. blood pressure ) and external stimuli (e.g. . when seeing , hearing , smelling ). Important biological processes that are essentially regulated by signal transduction include: a. Gene transcription , cell proliferation , immune response , olfactory perception , light perception and muscle contraction .
The start of a signal transduction process is initiated or triggered by an intracellular or extracellular stimulus.
Extracellular stimuli can be substances such as hormones , growth factors , extracellular matrix , cytokines , chemokines , neurotransmitters and neurotrophins . But nothing has been said about the molecular nature of these substances and the signaling molecules can be whole proteins , steroids or small organic molecules like serotonin . In addition, environmental stimuli can set the signal transduction in motion: electromagnetic waves (light) stimulate the cells in the retina , fragrances bind to olfactory receptors of olfactory cells in the nose, heat fluctuations are detected by sensory neurons and auditory hair cells react to mechanical stimuli ( sound waves ).
Intracellular stimuli such as B. calcium ion (Ca 2+ ), are often themselves part of signal transduction cascades.
Extracellular signals are recorded with the help of protein molecules in the membrane or in the cytosol of the cell, so-called receptors , and then converted into intracellular signals and processed. Receptors can be differentiated according to their location, structure and function.
Cytosolic receptors, such as steroid receptors , retinoid receptors and soluble guanylyl cyclase , are the primary targets of steroids , retinoids and small, soluble gases such as nitric oxide (NO) and carbon monoxide (CO), which pass through the cell membrane due to their lipophilicity and small molecule size can. Activation of steroid receptors leads, for example, to the formation of receptor dimers which, after binding to a response element , e.g. B. Sterol Response Element (SRE) act as transcription factors on the DNA itself .
Membrane-related receptors are proteins that, as transmembrane proteins, span a membrane and have both an outside and an inside domain. This enables them to bind signal molecules outside the cell and trigger a signal inside the cell through the associated change in conformation . The signal molecule does not pass the membrane, but binds to the extracellular domain, which leads to biochemical changes in the receptor molecule that also have an intracellular effect. The signal molecules are mostly hydrophilic substances in the aqueous medium, such as ions , neurotransmitters , peptide hormones or growth factors . These membrane receptors can be roughly assigned to three groups.
A distinction can be made between voltage-controlled, light-controlled and ligand-controlled ion channels . The latter are transmembrane proteins that are either activated or deactivated as a result of the binding of a ligand as a signal substance, whereby the permeability (permeability) of the membrane for certain ions is increased or decreased. This is particularly important when transmitting nerve signals to chemical synapses .
G protein coupled receptors
The signaling pathways via G proteins are among the best studied signal transduction pathways . They are involved in many sensory physiological processes, such as sight (via phototransduction ), smell and taste, as well as in the effects of numerous hormones and neurotransmitters. An activated G protein-coupled receptor works by stimulating the α subunit of a heterotrimeric G protein to exchange its bound GDP for GTP (i.e. a GTP exchange factor ), whereupon the G protein is divided into its subunits α and βγ decays (these two activated subunits then pass the signal on).
For example, G s / olf proteins activate adenylyl cyclase , which synthesizes the protein kinase A -activating second messenger cyclic adenosine monophosphate (cAMP). The G q / 11 proteins activate phospholipase C , which forms the second messengers inositol trisphosphate and diacylglycerol from membrane lipids. The G 12/13 proteins can regulate various other signal transduction pathways through activation of Rho-GTPase . The G i / o proteins can, on the one hand, inhibit adenylyl cyclase via their α-subunit and, on the other hand, stimulate phosphoinositide-3-kinase via their βγ-subunit .
Enzyme-Linked Signaling Pathways
Enzyme-coupled receptors are the third important group of cell surface receptors and can be divided into six classes:
- Receptor tyrosine kinases , which can activate the MAP kinase pathway and the PI3 kinase signal pathway , for example
- Tyrosine kinase-coupled receptors , which include many cytokine receptors that can activate the JAK-STAT signaling pathway , for example
- Tyrosine phosphatases , for which, among other things, the CD45 protein and SHP 1/2 are a substrate
- Receptor serine / threonine kinases , through which, for example, the TGF signaling pathway is activated
- Receptor guanylyl cyclases , which have guanylyl cyclase activity
- Histidine kinase-coupled receptors , which mediate chemotaxis in bacteria and were also found in plants (but not in animals)
Different signaling pathways can emanate from each of the above-mentioned receptor types. The transmission (transduction) of the external or internal signals picked up by a receptor to effector proteins within the cell is the actual task of signal transduction. This takes place through coordinated protein-protein interactions and an activation of intermediate signal proteins, which in turn can activate further intracellular signal proteins. During signal transduction, the signal is often amplified in that an activated protein molecule can activate several effector molecules. For example, a single photon- activated rhodopsin molecule (the photoreceptor in the retina responsible for vision) can activate up to 2000 transducin molecules.
The second messengers , which are secondary messenger substances of the cell metabolism, are of particular importance . Well-known examples are cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), inositol trisphosphate (IP 3 ), diacylglycerol (DAG) and calcium ions (Ca 2+ ). They represent intermediate stations in signal transduction and can in turn activate various signal pathways. They are therefore suitable as interfaces for various signal transduction pathways and play a major role in research into signal transduction processes. The many signal transduction pathways are linked to one another and also allow cell-specific reactions.
Modification of signal proteins
We now know various events that change the conformation of a signal protein:
- Phosphorylation by kinases or dephosphorylation by phosphatases ,
- the direct interaction between two proteins,
- the binding of the nucleotides GDP and GTP or cyclic nucleotides such as cAMP and cGMP as well
- other events such as calcium ion binding and acetylation .
Signal processes are often only made possible by the recruitment of signal proteins in specific cell compartments or by local accumulation and binding to their reaction partners (“signal complexes ”) or scaffolds (“scaffolds”).
Signal transmission through proteolysis
Some signaling pathways that are important in morphogenesis or apoptosis , for example , are based on proteolysis . Here, one signal protein splits another and thus leads to activation. Signaling pathways based on proteolysis include the Notch signal pathway , the Wnt signal pathway , the Hedgehog signal pathway , the NF-κB signal pathway and signaling pathways in apoptosis .
Activation of effector proteins
The aim of the signal transduction process is to activate effector proteins that trigger a specific cellular response. Effector proteins are, for example, transcription factors that activate the transcription of certain genes.
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