Signaling molecules that function within an organism to control metabolic processes within cells,...

Signaling molecules that function within an organism to control metabolic processes within cells, the growth and differentiation of tissues, the synthesis and secretion of proteins, and the composition of intracellular and extracellular fluids.

Extracellular signaling molecules are synthesized and released by signaling cells and produce a specific response only in target cells that have receptors for the signaling molecules.

Signal transduction.

The overall process of converting signals into cellular responses, as well as the individual steps in this process, is termed signal transduction.

Signal transduction pathways may involve relatively few or many components.

Communication by extracellular signals usually involves the following steps:

(1) synthesis and (2) release of the signaling molecule by the

signaling cell; (3) transport of the signal to the target cell; (4) binding of the signal by a specific receptor

protein leading to its activation; (5) initiation of one or more intracellular

signal-transduction pathways by the activated receptor;

(6) specific changes in cellular function, metabolism, or development;

(7) removal of the signal, which often terminates the cellular response

Endocrine, Hormones Paracrine, Growth factors Autocrine, Receptor Proteins Exhibit Ligand-

Binding and Effector Specificity.

Intracellular Signal Transduction

Many Conserved Intracellular Proteins Function in Signal Transduction

GTPase Switch Proteins

GPCRs & RGS

In mammals, twenty distinct genes for RGS proteins have been identified.

Protein Kinases and Phosphatases

At last count the human genome encodes 500 protein kinases and 100 different phosphatases.

In some signaling pathways, the receptor itself possesses intrinsic kinase or phosphatase activity; in other pathways, the receptor interacts with cytosolic or membrane associated kinases.

GPCRs

Regulation of glycogen metabolism

by cAMP in liver and muscle cells.

Amplification of an external signaldownstream from a cell-surface receptor.

G Protein–Coupled Receptors That Activate

Phospholipase C

Hormone binding to receptors coupled to either a Go or a Gq protein (see Table 13-1) induces activation of the isoform of phospholipase C (PLC).

Synthesis of DAG and IP3 frommembrane-bound phosphatidylinositol (PI).

Regulation..

The IP3-mediated rise in the cytosolic Ca2+ level is only transient because Ca2+ ATPases located in the plasma membrane and ER membrane actively pump Ca2+ from the cytosol to the cell exterior and ER lumen, respectively. Furthermore, within a second of its generation, one specific phosphate on IP3 is hydrolyzed, yielding inositol 1,4-bisphosphate, which does not stimulate Ca2+ release from the ER.

The activation of protein kinase C in different cells results in a varied array of cellular responses, indicating that it plays a key role in many aspects of cellular growth and metabolism.

In liver cells, for instance, protein kinase C helps regulate glycogen metabolism by phosphorylating and thus inhibiting glycogen synthase.

Protein kinase C also phosphorylates various transcription factors; depending on the cell type; these induce synthesis of mRNAs that trigger cell proliferation.