signaling proteins

Proteins and other molecules serve one or more of several types of function in signaling networks:
● cell surface
_ ● ion channels
_ ● receptor proteins
__ ● latent gene regulatory proteins
● intracellular
_ ● 'signaling' enzymes
_ ● adaptor proteins
_ ● amplifier proteins
_ ● anchoring proteins
_ ● bifurcation proteins
_ ● coincidence detectors
_ ● effector proteins
_ ● mediator molecules
_ ● messenger proteins
_ ● modulator proteins
_ ● relay proteins
_ ● scaffold proteins
_ ● second messengers
_ ● transducer proteins

Adaptor proteins link the components of signaling pathways by acting as accessories to the chief proteins in a signal transduction pathway.

Amplifier proteins are usually either enzymes or ion channels. Amplifiers increase the received signal by producing large amounts of small intracellular second messengers or by activating large numbers of downstream intracellular signaling proteins. Multiple amplification steps in a relay chain are often referred to as a signaling cascade.

Anchor proteins provide a molecular framework that orients these enzymes towards selected substrates. A-kinase anchoring proteins (AKAPs) are signal-organizing, scaffold proteins that compartmentalize the cAMP dependent protein kinase, phosphodiesterases, and a variety of enzymes that are regulated by second-messengers.

Bifurcation proteins spread the signal from one signaling pathway to others.

Coincidence detectors are signaling enzymes that are only activated by several different signals occurring together. For example, cAMP-generating adenylyl (adenylate) cyclases are modulated by G-proteins, forskolin, Ca2+/calmodulin, and other class-specific substrates.

Non-genetic classes of regulatory proteins include those target, effector proteins that are involved in special cellular functions such as signaling as receptor proteins and pumps, adhesion, chemotaxis, cellular transport and active transport, and metabolic regulation, including enzymatic action and protein degradation. Effector molecules bring about regulation by binding other molecules, and genetic effector molecules can participate in the regulation of gene expression. Modulator molecules bind to a regulatory sites during allosteric modulation, where effectors act as activators or inhibitors. (Allosteric proteins have an active (catalytic) site and an allosteric (effector) site.) Effector proteins regulate the activity of other proteins.

Integrator proteins integrate signals from two or more signaling pathways and relay the signal onward along a single pathway.

Latent gene regulatory proteins are activated by receptors at the cell surface and migrate to the nucleus, where they stimulate gene transcription.

Mediators act as molecular go-betweens in signaling cascades. Second messengers are small, readily diffusible molecules that operate in signal transduction (calcium ions, cAMP, cGMP, ceramide, diacylglycerol, inositol-1,4,5-trisphosphate).

Messenger proteins carry the signal from one part of the cell to another. For example, messengers often carry signals from the cytosol to the nucleus.

Modulator proteins regulate the activity of other proteins. Calmodulin (Ca2+-regulated modulator protein, CaM) is a ubiquitous eukaryotic intracellular calcium receptor that regulates the biological activities of many cellular proteins and transmembrane ion transporters. The Ca2+•calmodulin complex binds target proteins, initiating various signaling cascades.

Relay proteins pass the message to the next signaling component in the chain without otherwise participating.

Scaffold proteins either hold protein kinases in a latent state close to their activating cell-surface receptors, or facilitate flow of activation from one kinase to the next kinase in a signaling cascade. The A kinase anchoring proteins (AKAPs) are prototypical anchor/scaffold proteins that organize the protein kinases and phosphatases that regulate serine/threonine phosphorylation.

Transducer proteins convert the signal from one form to another. Signaling enzymes that produce cyclic AMP, for example, both convert the received signal and amplify it (transducer and amplifier).

'Signaling' domains are found in intracellular proteins that are involved in signaling cascades:
● EF hand domains
● PDZ domains
● pleckstrin homology (PH) domain family
● SH2 domains

Cell-surface adhesion interactions and inflammatory responses employ specialized domains:
● cadherin repeats
● carbohydrate-recognition domain (CRD)
● caspase recruiting domains, CARD domains
● C-lectin domain (CRD)
● C-type-lectin-like domain (CTLD)
● death domain (DD), death effector domain (DED) binds adaptor protein FADD (Fas-Associated Death Domain)
● zinc finger DNA binding domains