Introduction to Signal Transduction—Section 17.1
Related Technical Notes
Cells respond to their environment through a complex and interdependent series of signal transduction pathways that frequently begin at the cell membrane. Many cellular receptors are transmembrane proteins with extracellular domains that selectively bind ligands. In response to ligand binding, the receptor's cytoplasmic domain may change conformation and transmit the signal across the membrane, or individual receptors may aggregate and interact with other membrane proteins in order to generate a response. Transmembrane signals trigger a cascade of events in the cell, which can include changes in intracellular Ca2+ levels, enzymatic activity and gene expression (Figure 17.1.1).
We offer several important reagents for studying signal transduction mechanisms, including Ca2+ regulation and second messenger activities. This chapter focuses on probes for events occurring downstream from the receptor–ligand interaction. These products complement the probes for receptors and ion channels in Probes for Endocytosis, Receptors and Ion Channels—Chapter 16, as well as the many ion indicators discussed in Indicators for Ca2+, Mg2+, Zn2+ and Other Metal Ions—Chapter 19, pH Indicators—Chapter 20 and Indicators for Na+, K+, Cl– and Miscellaneous Ions—Chapter 21. Probes for Reactive Oxygen Species, Including Nitric Oxide—Chapter 18 describes our selection of probes for nitric oxide research—including nitric oxide donors, nitric oxide synthase inhibitors and reagents for nitrite detection—as well as for other reactive oxygen species.
Figure 17.1.1 Neurotransmitter receptors linked to second messengers mediating growth responses in neuronal and nonneuronal cells. Abbreviations: RAC/Gs = Receptors coupled to G-proteins that stimulate adenylate cyclase (AC) activity, leading to cAMP formation and enhanced activity of protein kinase A (PKA). RAC/Gi = Receptors coupled to pertussis toxin (PTX)–sensitive G-proteins that inhibit adenylate cyclase activity. RPLC = Receptors promoting the hydrolysis of phosphatidylinositol 4,5-diphosphate (PIP2) to inositol 1,4,5-triphosphate (IP3), which increases intracellular Ca2+, and diacylglycerol (DAG), which activates protein kinase C (PKC). RION = Receptors indirectly promoting ion fluxes due to coupling to various G-proteins. RLG/ION = Receptors that promote ion fluxes directly because they are structurally linked to ion channels (members of the superfamily of ligand-gated ion channel receptors). Stimulation of proliferation is most often associated with activation of G-proteins negatively coupled to adenylate cyclase (Gi), or positively coupled to phospholipase C (Gq) or to pertussis toxin–sensitive pathways (Go, Gi). In contrast, activation of neurotransmitter receptors positively coupled to cAMP usually inhibits cell proliferation and causes changes in cell shape indicative of differentiation. Reprinted and modified with permission from J.M. Lauder and Trends Neurosci (1993) 16:233.