Agriculture Reference
In-Depth Information
2 eptides as signals
Yiji Xia
2.1
Introduction
Peptides are a major class of signal molecules in animals that regulate a wide variety
of physiological and developmental processes. The first peptide hormone, insulin,
was discovered in 1922 (Banting & Best, 1922). Like other hormones, insulin is
produced in specific organs (endocrine glands), is released into the bloodstream,
and acts on distant target cells to regulate glucose metabolism. The subsequent
discovery of a large number of other peptide hormones in animals was aided by the
relative ease in isolating the specific hormone-producing organs and tissues such
as the pituitary gland, the pancreas, and the thyroid, as well as the availability of
biological assays for their activities. Although most peptide hormones are small,
some peptide hormones are relatively large, with a size of up to 300 amino acids
(Habener, 1987).
Peptide hormones are generally synthesized as inactive precursors that undergo
proteolytic processing in the endoplasmic reticulum (ER) and Golgi apparatus to
form mature hormones. Mature hormones are then released by exocytosis and en-
ter the bloodstream in secretory granules. Peptide hormones are polar molecules
that cannot diffuse easily through the plasma membrane and, therefore, usually
do not enter target cells. Peptide signals are perceived on the cell surface by cog-
nate receptors and the signals are then relayed through second messengers to con-
vert the extracellular signals into intracellular physiological responses. The largest
family of cell surface receptors in animals is the G-protein-coupled receptor (GPCR)
family that are characterized by seven-transmembrane-segment (STMS) topogra-
phy (Neves
et al.
, 2002). Binding of a hormone to GPCR activates a heterotrimeric
guanyl nucleotide-binding protein (G-protein). G-protein then activates a variety of
effectors, including adenylate cyclase that catalyzes the formation of cyclic AMP
(cAMP) and phospholipases that catalyze the phosphoinositide signaling cascade.
Many peptide hormones exert their effects by binding to receptors that have
tyrosine kinase activity in their intracellular domains. The ligand binding results
in dimerization of such a receptor tyrosine kinase (RTK) and leads to autophos-
phorylation and then phosphorylation of cytoplasmic target proteins (Schlessinger,
2000). The RTK signaling pathways are often mediated by a monomeric G-protein
named Ras. Binding of the cognate ligand to RTK activates Ras, which then relays
the signal through a kinase cascade to activate mitogen-activated protein kinases
(MAPKs). Activated MAPKs translocate from the cytosol to the nucleus to activate
transcription factors.
