Signal transduction

As signal transduction or signal conversion, signal transmission or signal transmission are called processes in biochemistry and physiology, means of which cells react for example to external stimuli, convert them forward as a signal into the cell interior and run through a signal chain for cellular effect. In these processes is often a large number of enzymes and secondary messengers ( second messengers ) are involved in one plane or on several successively connected ( signal transduction ). In this case, the original signal can be significantly enhanced under certain circumstances ( signal amplification ). Signals of different signal paths are often related to one another and integrated by means of " cross-talk " in the cytoplasm or in the nucleus. The sum of all pathways in one cell type is also known as the signaling network. Signaling networks are plastic and vary, for example, in various stages of development of an organism.

Signal transduction processes are single-celled organisms essential to respond to changes in their environment, for example through regulation of metabolism and gene expression can and to ensure the survival. In multicellular organisms, the cellular signal transduction in addition, a key step in the processing of signals that are communicated via extracellular messengers such as hormones and neurotransmitters, as well as for recording internal (eg blood pressure) and external stimuli (eg. seeing, hearing, smelling ). Important biological processes that are regulated substantially above signal transduction, are, inter alia, gene transcription, cell proliferation, immune response, sense of smell, perception of light, and muscle contraction.

• 3.1 Second Messenger
• 3.2 modification of signaling proteins
• 3.3 signaling by proteolysis

Stimulation

The beginning of a Signaltransduktionsprozesses is initiated or triggered by an intracellular or extracellular stimulus.

Extracellular stimuli may be substances such as hormones, growth factors, extracellular matrix, cytokines, chemokines, neurotrophins, and neurotransmitters. Here, however, nothing has been said about the molecular nature of these substances and the signal molecules there may be whole proteins, steroids or small organic molecules such as serotonin. In addition, environmental stimuli can set the signal transduction in response: electromagnetic waves (light ) stimulate the cells in the retina, fragrances bind to odorant receptors in the nose, heat fluctuations are detected by sensory neurons and auditory hair cells respond to mechanical stimuli ( sound waves).

Intracellular stimuli, such as calcium ions ( Ca2 ), are often themselves part of signal transduction cascades.

Reception

With the aid of proteins in the cell membrane and within the cell ( receptor ) extracellular signals are received and processed inside the cell. These receptors can be classified according to their localization to distinguish their structure and function.

Cytosolic receptors

Cytosolic receptors, such as the steroid receptors, retinoid receptors and the soluble guanylyl cyclase, are the primary targets of steroids, retinoids and small, soluble gases such as nitric oxide ( NO) and carbon monoxide ( CO) that happen due to their lipophilicity and their small molecular size, the cell membrane can. Activation of steroid receptor, for example, leads to formation of receptor dimers that act by binding to a response element, such as the sterol response element (SRE ) on the DNA itself as the transcription factors.

Membrane -bound receptors

Membrane -bound receptors ( transmembrane receptors) are proteins which possess both an extracellular domain and an intracellular domain ( and in between at least one transmembrane segment). Thus, they are able to bind signal molecules external to the cell and to pass through a conformational change, the signal into the cell. It is important to mention that the signal molecule itself does not penetrate the membrane, but the biochemical changes are due solely to the activity of the receptor. It is in these signaling molecules mostly hydrophilic substances, such as ions, neurotransmitters, peptide hormones and growth factors. The membrane receptors can be roughly divided into three groups:

Ion channels

Here we can distinguish voltage-gated and ligand-gated ion channels. Here are transmembrane proteins, which are due to a signal either on or off and thus the permeability ( permeability ) to increase or decrease the membrane to certain ions. This is especially of great importance for the transmission and amplification of nerve signals.

G- protein coupled receptors

→ Main article: G- protein - coupled receptor

Among the most studied signal transduction pathways include the signal paths via G proteins. They are of physiological processes, such as seeing ( on the visual signal transduction), smell and involved in the action of numerous hormones and neurotransmitters. The activated G protein- coupled receptor acts in that it stimulates the α - subunit of a heterotrimeric G- protein, it bound GDP exchange for GTP ( thus affects the receptor as GEF: Guanine nucleotide exchange factor, GTP exchange factor ), whereupon the G-protein α and βγ disintegrates into its subunits (these two active sub-units then pass the signal on).

For example, activate Gs / olf proteins adenylyl cyclase, which synthesizes the protein kinase A- activating second messenger cyclic adenosine monophosphate ( cAMP). Gq/11-Proteine ​​activate phospholipase C, which forms from membrane lipids, the second messenger inositol trisphosphate and diacylglycerol. The G12/13-Proteine ​​can adjust various other signal transduction pathways via activation of Rho- GTPase. Gi / o proteins, on the one hand inhibit adenylyl cyclase via its α - subunit, and on the other hand, stimulate the phosphoinositide 3-kinase via its βγ subunit.

Enzyme-linked signaling pathways

Enzyme - coupled receptors are the third important cell surface receptors and can be divided into six classes:

• Receptor tyrosine kinases which, for example, activate the MAP kinase pathway and the PI3- kinase pathway.
• Tyrosine kinase -coupled receptors. These include many cytokine receptors such as the activate the JAK -STAT signaling pathway.
• Tyrosine phosphatases, which have, among other things, the CD45 protein and SHP1 / 2 as a substrate.
• Rezeptor-Serin/Threoninkinasen. Through them, the TGF- signaling pathway is activated, for example.
• Receptor guanylyl cyclases, which have Guanylylcylcase activity
• Histidine kinase - coupled receptors act mainly in bacteria and plants ( not found in animals )

Signal transduction

From each of the above types of receptors different signaling pathways can expect. The forwarding ( transduction ) the power absorbed by a receptor external or internal signals to effector proteins within the cell is the actual task of signal transduction. This is done through coordinated protein-protein interactions and activation of intermediary signaling proteins which in turn can activate other intracellular signaling proteins. During signal transduction, the signal is often amplified by an activated protein molecule can activate multiple effector molecules. For instance, activate up to 2000 Transducinmoleküle a single photon by a Rhodopsinmolekül activated ( the photoreceptor in the retina that is responsible for vision ).

Second Messenger

Particular importance is attached to the second messengers that are second messengers in cellular metabolism. Well-known examples are cyclic adenosine monophosphate ( cAMP), cyclic guanosine monophosphate (cGMP ), inositol triphosphate (IP3 ), diacylglycerol (DAG ) and calcium ions ( Ca2 ). They represent intermediate stations in signal transduction and may in turn activate different signaling pathways. They are therefore suitable as an interface for different signal transduction pathways and play a major role in the research of signal transduction. The many signal transduction pathways are interconnected and also allow cell-specific responses.

Modification of signaling proteins

We know now different events that alter the conformation of a protein signal:

Signal processes are often only through recruitment of signaling proteins in specific cell compartments or by local accumulation and binding to its reaction partner ( " signaling complexes " ) and scaffold proteins ( " scaffolds " ) allows.

Signaling by proteolysis

Some, such as morphogenesis or apoptosis important signaling pathways based on proteolysis. Here, a signal protein cleaves another, thus leading to activation. Signal paths which are based on proteolysis, inter alia, the Notch signaling pathway, the Wnt signaling pathway, the hedgehog signaling pathway, the NF-KB pathway, and pathways of apoptosis.

Activation of effector

The aim of the Signaltransduktionsprozesses is the activation of effector proteins that trigger a specific cellular response. Effector, for example, transcription factors activate the transcription of certain genes.