Signal Transduction

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See also Receptors    See also Enzyme linked receptors See also Toll-like Receptors

The detection and interpretation of signals from the environment are necessary features of all cells. Although there are an enormous number of different signal-transduction pathways, some very common processes include the following:

• Signal/receptor interaction: signal transduction starts with the interaction between a signal and its receptor. Signals which cannot penetrate the cell membrane like water soluble molecules and membrane bound ligands (such as MHC-peptide complexes) bind to receptors on the surface of the cell membrane. Hydrophobic signals, such as steroids, that can diffuse through the cell membrane are bound by intracellular receptors.

• G proteins: Signals are often transduced through G proteins.

• Second messengers: Signal reception often leads to the generation within the cell of a "second messenger" that can diffuse to other sites in the cell and evoke changes. Examples are cylcik nucleotides (cAMP, cGMP), calcium ion and membrane phospholipid derivatives like diacylglycerol (DAG) and inositol triphosphate (IP3)

• Protein kinases and phasphatases are activated or inhibited. Kinases catalyze the phosphorylation of target residues (tyrosine, serine, or threonine) of key elements in many signal transduction pathways. Protein phosphorylation is used in many different ways to control the activity of transcription factors. It directs subcellular localization, selectively controls binding of dimerization partners (e.g., signal transducers and activators of transcription), or alters transcriptional activity by facilitating the interaction with components of the transcriptional machinery (e.g., cyclin AMP-responsive element binding protein, p53 and NFkB. Phosphatases catalyze deposphorylation, reversing the effect of kinases.

• Adaptor proteins often bind specifically and simultaneously to 2 or more different molecules with signaling roles, bringing them together and promoting their combined activity.

• Signals are amplified by enzyme cascade. Each enzyme in the cascade catalyzes the activation of many copies of the next enzyme in the sequence, greatly amplifying the signal at each step and providing many ways to modulate the intensity of the signal along the way.

• The default setting for signal transduction pathways is usually off. In the absence of an appropriately presented signal, transmission through the pathway does not take place.

• Activation of Transcription Factors is one of the most common responses to receptor engagement. Among the transcription factors, the active heterodimer p50/p65 form of nuclear factor (NF)-Κβ plays a central role in immunological process by inducing expression of a variety of genes involved in inflammatory responses. Other transcription factors are regulated by signal transduction pathways that involve enzymatic cascades of mitogen-activated protein (MAP) kinases which are activated by many receptors and environmental stresses.