Receptor Signal Transduction

Protein receptors bind specific ligands as the initial step in signal transduction to participate in cellular signaling, gene regulation, cellular proliferation, cellular differentiation, or regulation of cellular metabolic processes. A ligand is any molecule that binds reversibly to a specific site on a protein, and can be nucleic acids, polysaccharides, lipids, hormones, neurotransmitters, amino acids, peptides, polypeptides, or another proteins. Ligand-protein binding may be simple, allosteric, or competitive. Metabotropic receptors are coupled to G proteins, acting through various secondary pathways involving ion channels, enzymes such as adenylyl (adenylate) cyclases, and phospolipases, or PDZ domains. Ionotropic receptors are ligand-activated ion channels that permit entry of ions when the central pore is open.

Plasma membrane receptors

Receptor family [iuphar]

Ligands

Functions

cytokine receptors = G- protein Cytokines of immune response Metabotropic receptor
Guanine nucleotide-binding protein-coupled receptors (GPCRs) of GPCR families

Neurotransmitters : acetylcholine, dopamine, epinephrine, GABA, glutamate, serotonin. Nucleoside : adenosine. Hormones : angiotensin, cholecystokinin, glucagon, secretin, somatostatin. Cytokines chemokines. Histamines - H1,2,3,4. Cannabinoids and Opioids. Sensory stimuli - olfaction, vision. Calcium.

Metabotropic / sensory
Guanylyl cyclase receptors ANP and natriuretic peptides (GC-A & GC-B), Guanylin (GC-C) Metabotropic. Guanylyl cyclases convert GTP to the second messenger, cGMP.
integrins
neurotransmitter ion channels Neurotransmitters: acetylcholine, GABA, glutamate, glycine, serotonin Ionotropic
receptor tyrosine kinases (RTKs): EGFR, Tie receptors, Eph RTKs, IGF-1 growth factors, insulin, erythropoietin, cytokines Metabotropic
TGF-β receptors; activin, BMP: associated with serine/threonine kinases: MAPK cascade; phosphoinositol kinase-related kinase (PIKK) family - mTOR (FRAP1), ATM, ATR, DNA-PK growth factors, transforming growth factor β, mitogens, leucine, insulin, nutrients → Ras, phosphatidylinositol-3-OH kinase
TNF receptors FasL (pro-apoptotic protein induced by DNA damage) Fas-associated death domain protein (FADD) regulation of apoptosis.

Intracellular receptors

Ligand to cytoplasmic receptor

Actions

steroid hormones: bind transcription factor receptors. Type I HREs: sex hormones, glucocorticoids, mineralocorticoids. Type II nuclear receptors: thyroid hormone, vitamins A & D, retinoid. Orphan receptors. alter gene expression
inositol trisphosphate (IP3) release of stored second messenger calcium ions
sigma1: neuroactive steroids (neurosteroids) allosteric modulators of neurotransmitter receptors: DHEA, PREG, PROG, PROG-R alter neuronal excitability through interaction with neurotransmitter-gated ion channels

Signaling pathways

mitogen-activated protein kinase (MAPK)/Ras signaling cascades
phosphatidyl inositol-3-kinase (PI3K)/AKT
protein kinase C

Specific genes encoding receptors

Gene

Receptor

Function

FAS gene TNFRSF6 - tumor necrosis receptor 6 apoptosis

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. . . since 10/06/06