![]() Targeting the apoptosis pathway in hematologic malignancies. Apoptosis and molecular targeting therapy in cancer. ![]() Apoptosis: a review of programmed cell death. Apoptosis: a basic biological phenomenon with wideranging implications in tissue kinetics. Cytology of degeneration in the intersegmental muscles of the Pernyi silkmoth. These mechanisms ensure that the cellular response is controlled by inhibiting the flow of information, and stalling the cellular response even after cellular detection of a given signal.Lockshin RA, Williams CM. In another mechanism, Ca2+ ions are pumped back into calcium stores by pumps, thus restoring their normal concentrations in the cytosol. This occurs, for example, with lipids such as IP3 which are metabolized by inositol phosphatases, and cyclic AMP / cyclic GMP which are degraded by phosphodiesterases. The intracellular signaling molecules can also be degraded. This may be achieved via a number of mechanisms.įor example, receptors may be desensitized to the ligand, as is commonly seen for ion channels. Instead many signal pathways are controlled by ‘molecular switches’ that can switch off a given response should they become detrimental to the required cell state or function. ![]() Off mechanismsĬells do not respond to any one signal continuously. These may promote processes such as exocytosis, endocytosis, migration, actin remodeling, gene expression, etc.Įxamples include transcription factors which induce gene expression or actin binding proteins which induce actin remodeling, cell migration, etc. Sensors and effectorsĬonsidered the final stage in the signaling pathway or cascade, the sensor and effector proteins are responsible for the cell’s response to the signal. Instead, each intracellular messenger will act within a larger signaling pathway. It should be noted that it is rare for these molecules to function alone. One key superfamily of intracellular messengers are the Small GTPases. Examples of intracellular messengers include calcium ions, enzymes such as adenylyl cyclase, or lipids such as inositol triphosphate, etc. For every one receptor that is activated, multiple intracellular messenger molecules are activated and therefore it is at this stage that the signal is said to be amplified. Intracellular messengers, or secondary messengers, are the intermediate proteins or small molecules that carry a signal from the receptor to intracellular sensors and effectors. Nitric oxide gas and steroids like estrogen are examples of such ligands. These receptors are activated by hydrophobic ligands that can pass through the lipid membrane and therefore enter the cell passively. It should be noted that intracellular receptors, such as steroid receptors, are also relevant to signal transduction. Being associated with electrical signaling, ion channels are most commonly observed in muscle and brain cells. Ion channels usually transport a specific type of ion, with Na+, K+, Ca2+ and Cl- being the most common that are associated with ‘information flow’ or signal transduction. In this case however, the protein will acquire an open conformation that permits the ions to flow into the cell. Similarly, activation of an ion channel also occurs through interactions with a ligand and also induces a conformational change within the protein. Activation of GPCRs, which results from GDP to GTP exchange within this linked G-protein, subsequently activates a range of kinases which in turn facilitate phosphorylation events on target proteins. Receptors can be broadly classified into three categories.Īs the name suggests, GPCRs are linked to a monomeric or trimeric G-protein via their cytosolic domain. These signal cascades pass the signal from one molecule to another before a cellular response is achieved Binding of a ligand to the extracellular region of a receptor often initiates a conformational change within the cytosolic domain and this initiates a series of biochemical reactions known as signal cascades. These proteins are most often transmembrane, with an extracellular domain for ligand binding and an intracellular domain that is often chemically linked to a downstream signaling pathway. Receptors are proteins that interact with specific ligands and transmit the resulting signals to the cell interior. In some cases the protein components may serve as receptors, in other cases they may act as intracellular messengers, or, they may serve as sensors or effectors. Although the full array of individual molecules cannot be discussed in detail here, the functions or roles that they play can be described. There are many components that facilitate cell signaling.
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