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Signal transduction

This article is about signaling at the cellular level. For systemic signal transduction, see Transduction (physiology).

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 is catalyzed by protein kinases, ultimately resulting in a cellular response. Proteins responsible for detecting stimuli are generally termed receptors, although in some cases the term sensor is used.[1] 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 known as a signaling pathway.

When signaling pathways interact with one another they form networks, which allow cellular responses to be coordinated, often by combinatorial signaling events.[2] At the molecular level, such responses include changes in the transcription or translation of genes, and post-translational and conformational changes in proteins, as well as changes in their location. These molecular events are the basic mechanisms controlling cell growth, proliferation, metabolism and many other processes.[3] In multicellular organisms, signal transduction pathways regulate cell communication in a wide variety of ways.

Each component (or node) of a signaling pathway is classified according to the role it plays with respect to the initial stimulus. Ligands are termed first messengers, while receptors are the signal transducers, which then activate primary effectors. Such effectors are typically proteins and are often linked to second messengers, which can activate secondary effectors, and so on. Depending on the efficiency of the nodes, a signal can be amplified (a concept known as signal gain), so that one signaling molecule can generate a response involving hundreds to millions of molecules.[4] As with other signals, the transduction of biological signals is characterised by delay, noise, signal feedback and feedforward and interference, which can range from negligible to pathological.[5] With the advent of computational biology, the analysis of signaling pathways and networks has become an essential tool to understand cellular functions and disease, including signaling rewiring mechanisms underlying responses to acquired drug resistance.[6]

Simplified representation of major signal transduction pathways in mammals.
  1. ^ Bradshaw RA, Dennis EA, eds. (2010). Handbook of Cell Signaling (2nd ed.). Amsterdam, Netherlands: Academic Press. ISBN 9780123741455.
  2. ^ Papin JA, Hunter T, Palsson BO, Subramaniam S (February 2005). "Reconstruction of cellular signalling networks and analysis of their properties". Nature Reviews. Molecular Cell Biology. 6 (2): 99–111. doi:10.1038/nrm1570. PMID 15654321. S2CID 3065483.
  3. ^ Krauss G (2008). Biochemistry of Signal Transduction and Regulation. Wiley-VCH. p. 15. ISBN 978-3527313976.
  4. ^ Reece J, Campbell N (2002). Biology. San Francisco: Benjamin Cummings. ISBN 978-0-8053-6624-2.
  5. ^ Kolch W, Halasz M, Granovskaya M, Kholodenko BN (September 2015). "The dynamic control of signal transduction networks in cancer cells". Nature Reviews. Cancer. 15 (9): 515–27. doi:10.1038/nrc3983. PMID 26289315. S2CID 35252401.
  6. ^ Bago R, Sommer E, Castel P, Crafter C, Bailey FP, Shpiro N, Baselga J, Cross D, Eyers PA, Alessi DR (2016) The hVps34-SGK3 pathway alleviates sustained PI3K/Akt inhibition by stimulating mTORC1 and tumour growth. EMBO Journal 35:1902-22

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