Cell Signalling and G-protein

A cell’s ability to respond to its environment is essential to its survival. Short term-responses to environmental stimuli, which can occur rapidly and are usually reversible, most often result from modification of existing proteins. The long-term response, are usually the result of changes in the transcription of genes. Extracellular signals that induce long-term responses to affect many aspects of cell function; division, differentiation, and even communication with other cells.

Alterations in these signaling pathways cause many human diseases including cancer, diabetes, and immune defects. In order to illustrate the variety of mechanisms used to activate key transcription factors, the eight classes of cell surface receptors and the intracellular signal pathways that they activate area important. Ligand binding to many receptors causes activation by inducing two or more receptor molecules to form a complex on the cell surface. Most signaling pathways involve one or more protein Kinases.

Many extracellular signaling molecules are synthesized and released by signaling cells within the organism. In all cases, signaling molecules produce a specific response only in target cells that have receptors for the signaling molecules. Many types of chemicals are used as signals: small molecules, peptides, soluble proteins, and many proteins presented to the surface of a cell or found to the extracellular matrix. Most receptors bind a signal molecule are a group of closely related molecules.

Most signaling molecules, however, are too large and too hydrophilic to penetrate through the plasma membrane. These bind to cell surface receptors that are integral proteins on the plasma membrane. Cell surface receptors generally consist of three discrete segments: a segment on the extracellular surface, a segment that spans the plasma membrane and a segment facing the cytosol.

The signaling molecules act as a ligand which binds to a structurally complementary site on the extracellular or membrane-spanning domains of the receptors. Binding of the ligand induces a conformational change in the receptor that is transmitted through the membrane-spanning domain to the cytosolic Domain resulting in binding to and subsequent activation of other proteins in the cytosol or attached to the plasma membrane. The overall process of converting extracellular signals into intracellular responses as well as the individual steps in these processes is termed as Signal transduction. The molecules involved in the process is called Signal transducers.

Most ligands are responsible for cell-cell signaling (including neurotransmitters, peptide hormones, and growth factors) bind to receptors on the surface of their target cells. A major aspect in understanding the cell-cell signaling is understanding the mechanisms by which cell surface receptors transmit the signals initiated by ligand binding.

Cell surface receptors, including the receptors for peptide hormones and growth factors, act instead by regulating the activity of intracellular proteins. These proteins then transmit signals from the receptor to a series of additional intracellular targets, frequently including transmission factors. Ligand binding to a receptor on the surface of the cell thus initiates a chain of intracellular reactions, ultimately reaching the target cell nucleus and resulting in programmed changes in Gene Expression.

The largest family of cell surface receptor transmits a signal to intracellular targets via the intermediary action of guanine nucleotides binding proteins called G proteins. Nearly thousand such G protein-coupled receptors have been identified including the receptors for Eicosanoids, many neurotransmitters, neuropeptides, and peptides hormones. In addition, the G-Protein coupled receptor family includes a large number of receptors that are responsible for smell, site, and taste

The G-Protein Coupled receptors are structurally and functionally related proteins characterized by seven membrane-spanning alpha helices. The binding of Ligands to the extracellular domains of these receptor induces a conformational change that allows the cytosolic domain of the receptors to activate a G-Protein associated with the inner phases of the plasma membrane. The activated G-protein then dissociates from the receptors and carries the signal to an intracellular target, which may be either an enzyme or an ion channels.