SIGNAL TRANSDUCTION

General Principles: Signal Transduction

Communication between cells receive a signal transmit the signal within the cell alter behavior to fit signal

A simple intracellular signaling pathway activated by an extracellular signal molecule influences cell behavior.
Signal molecule
binds

receptor
activates

Intracellular signaling pathway

Target protein

alters cell behavior

General Principles: signaling molecules and their receptors

Cells communicate by means of hundreds of kinds of signaling molecules

Examples of types of signaling molecules: proteins, small peptides, amino acids, nucleotides, steroids, retinoids, fatty acid derivatives, dissolved gasses.

Signaling molecules are produced by signaling cells Regardless of the type of signal, the target cell responds using a receptor, which specifically binds to the signal molecule and initiates a response.

General Principles: signaling molecules and their receptors

Extracellular Signals -recognized by specific receptors. Hydrophilic: unable to cross the plasma membrane - bind to cell-surface receptors Example: growth factors Hydrophobic: pass across the cell membrane and directly regulate the activity of an intracellular receptor. -transported via carrier proteins Example: Steroid hormones, thyroid hormones, vitamin D bind to intracellular receptors that are ligand-activated transcription factors.

cell surface receptors

cell

intracellular receptors

cell

Each cell is programmed to respond to specific combinations of signaling molecules. Typical mammalian cell is exposed to hundreds of different signals -respond selectively Each cell has a set of receptors Receptors allow cell to respond to a set of signal molecules Signal molecules work in combination

General Principles of Cell Signaling There are three known classes of cell-surface receptor proteins: Ion-channel-linked G-protein-linked Enzyme-linked
Ion-channel-linked receptors also known as transmitter-gated ion channels. G-protein-linked receptors also known as serpentine receptors enzyme-linked receptors -enzymes: tyrosine kinases -directly associate with an enzyme that they regulate

Cell-surface receptors Act as signal transducers: they bind the signaling ligand with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell.

Activated cell surface receptors trigger a phosphorylation cascade which results in signal relay through the cell and to the nucleus.

Ion-channel-linked receptors
Ion-channel-linked receptors, also known as transmittergated ion channels, are involved in rapid synaptic signaling between electrically excitable cells,. This type of signaling is mediated by a small number of neurotransmitters that transiently open or close the ion channel formed by the protein to which they bind.

closed

open

ligand

ions

G-protein-linked receptors
Receptor The interaction between the G-protein-linked receptor and the target is mediated by a trimeric GTP-binding regulator protein (Gprotein). All of the G-protein-linked receptors belong to a large superfamily of homologous, seven-pass transmembrane proteins.

Trimeric GTP-binding protein

Receptor tyrosine kinases

Single-pass transmembrane proteins ligand-binding site outside the cell catalytic site inside. The binding of growth factors such as insulin, epidermal growth factor to the extracellular domain of their receptors switches on the kinase activity of their catalytic domain and triggers phosphate group additions to a network of intracellular proteins to transduce the signal.

major signaling mechanisms share common features In both receptor tyrosine kinase signaling and Gprotein-mediated signaling, a signaling protein is activated by the addition of a phosphate group and inactivated by the removal of the phosphate.

Signaling by phosphorylation

Signaling by GTP-binding protein

Signal Transduction: General Principles Summary Cell signaling requires both extracellular signaling molecules and a complementary set of receptor proteins in each cell. Most signaling molecules are hydrophilic and activate cell surface receptors. There are three main families of cell surface receptors. The highly regulated phosphorylation cascade stimulated by activated receptors relays the signal through the cytoplasm and to the nucleus to alter cellular behavior.

Signaling molecules -hydrophobic -hydrophilic

Receptors -specific - intracellular - cell surface

Ion-channel-linked receptors

G-protein-linked receptors
enzyme-linked receptors