Cell Signaling

(Lodish et al., 2000, Section 20.1 )

Cells communicate by means of extracellular signaling molecules. These molecules are released by signaling cells and produce a specific response only in the target cells that have receptors for the signaling molecules. This process is called signal transduction.

Communication usually involves six steps:

Synthesis of the signaling molecule.
Release of the signaling molecule.
Transport of the signaling molecule.
Binding of signaling molecule to receptor on/in target cell.
Cellular response to signal molecule.
Removal of the signal.

Signaling in animals can be classified into three types depending on the distance over which the signal acts (Fig. 20.1a-c). Additionally, non-secreted, membrane bound signals can directly signal adjacent cells (Fig. 20.1d).

Signaling Type	Example of Signaling Molecule
Endocrine Signaling	hormones, epinephrine, epidermal growth factor (cleaved from membrane)
Paracrine Signaling	neurotransmitters, epinephrine
Autocrine Signaling	growth factors, epidermal growth factor (membrane bound)

Receptor proteins recognize and bind to the signaling molecules called ligands.
Receptors can be located in the cytosol or on the cell surface (Fig. 20.2).
Binding of the ligand to the receptor causes an altered cell response often resulting in altered transcription of specific genes (Fig. 20.2).

Cell-surface receptors can be grouped into four major classes (Fig. 20.3):

G protein-coupled receptors. -> produce second messengers like cAMP, PIP2, DAG (Fig. 20.4).
Ion-channel receptors. -> bind of ligand opens channel and allows ions to flow into cell.
Tyrosine kinase-linked receptors. -> activates protein kinases.
Receptors with intrinsic enzymatic activity. -> often act as protein kinases, some autophosphorylate.

Molecules in the signaling response pathway must be able to return to he non-signaling state (Fig. 20.5). Active and inactive states can be determined by :

Association with GTP/GDP (Fig. 20.5a).
Phosphorylation (Fig. 20.5b).
Protein confirmation (Fig. 20.5c).

Signaling is often associated with complex response pathways (Fig.20.6).
Common signaling pathways can be initiated by different receptors (Fig.20.6).

Examples of different mammalian hormones and their properties (Table 20.1).

Activity

Quiz

References:
Lodish, H., Berk, A., Zipursky, S.L., Matsudaira, P., Baltimore, D., Darnell, J., 2000, Molecular Cell Biology, 4th Ed., W.H. Freeman and Company, NY, New York. ISBN 0-7167-3136-3.