G protein GTPase-activating proteins

Regulation of speed, amplitude, and signaling selectivity

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42 Citations (Scopus)

Abstract

Numerous hormones of every chemical class use G protein-mediated signaling pathways to convey information from their receptors on the cell surface to the effector proteins that propagate these signals within the target cell. G proteins convey information from receptor to effector by traversing a controlled cycle of activation deactivation. When a receptor binds hormone, it promotes the binding of GTP to a select subset of the G proteins on the inner face of the plasma membrane. GTP binding activates these G proteins and allows them in turn to activate one or more effector proteins. G protein activation is terminated when a G protein hydrolyzes bound GTP to GDP; GDP remains bound but does not activate (for review see Kaziro et al., 1991). Cells use this basic pathway - receptor → G protein → effector - to form a complex information-processing network in the plasma membrane (Fig. 1). A cell responds to selected hormones by expressing appropriate receptors, which may be highly selective for a single G protein or may activate multiple G proteins. Expression of receptor isoforms that are selective for different G proteins can generate diverse cellular signals in response to a single hormone. At the next level in the network, a G protein (some cells express six or more) may respond to several different receptors, one G protein may activate or inhibit one or more of at least a dozen effector proteins. Effectors include enzymes that generate or degrade second messengers (adenylyl cyclase, cyclic GMP phosphodiesterase, phosphoinositide-specific phospholipase C-βs), ion channels (for Na+, Ca2+, or K+), and, probably, transport proteins. As at the previous two levels, effector isoforms respond selectively to distinct G proteins. G protein networks are thus analog computers that propagate an array of cellular signals in response to stimulatory and inhibitory hormones in the milieu of the target cell.

Original languageEnglish (US)
Pages (from-to)207-221
Number of pages15
JournalRecent Progress in Hormone Research
Volume50
Issue number1
StatePublished - 1995

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GTPase-Activating Proteins
GTP-Binding Proteins
Hormones
Guanosine Triphosphate
Protein Isoforms
Analogue Computers
Cell Membrane
Phosphoinositide Phospholipase C
Proteins
Information Services
Cyclic GMP
Phosphoric Diester Hydrolases
Cell Surface Receptors
Second Messenger Systems
Automatic Data Processing
Ion Channels
Adenylyl Cyclases

ASJC Scopus subject areas

  • Endocrinology

Cite this

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title = "G protein GTPase-activating proteins: Regulation of speed, amplitude, and signaling selectivity",
abstract = "Numerous hormones of every chemical class use G protein-mediated signaling pathways to convey information from their receptors on the cell surface to the effector proteins that propagate these signals within the target cell. G proteins convey information from receptor to effector by traversing a controlled cycle of activation deactivation. When a receptor binds hormone, it promotes the binding of GTP to a select subset of the G proteins on the inner face of the plasma membrane. GTP binding activates these G proteins and allows them in turn to activate one or more effector proteins. G protein activation is terminated when a G protein hydrolyzes bound GTP to GDP; GDP remains bound but does not activate (for review see Kaziro et al., 1991). Cells use this basic pathway - receptor → G protein → effector - to form a complex information-processing network in the plasma membrane (Fig. 1). A cell responds to selected hormones by expressing appropriate receptors, which may be highly selective for a single G protein or may activate multiple G proteins. Expression of receptor isoforms that are selective for different G proteins can generate diverse cellular signals in response to a single hormone. At the next level in the network, a G protein (some cells express six or more) may respond to several different receptors, one G protein may activate or inhibit one or more of at least a dozen effector proteins. Effectors include enzymes that generate or degrade second messengers (adenylyl cyclase, cyclic GMP phosphodiesterase, phosphoinositide-specific phospholipase C-βs), ion channels (for Na+, Ca2+, or K+), and, probably, transport proteins. As at the previous two levels, effector isoforms respond selectively to distinct G proteins. G protein networks are thus analog computers that propagate an array of cellular signals in response to stimulatory and inhibitory hormones in the milieu of the target cell.",
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N2 - Numerous hormones of every chemical class use G protein-mediated signaling pathways to convey information from their receptors on the cell surface to the effector proteins that propagate these signals within the target cell. G proteins convey information from receptor to effector by traversing a controlled cycle of activation deactivation. When a receptor binds hormone, it promotes the binding of GTP to a select subset of the G proteins on the inner face of the plasma membrane. GTP binding activates these G proteins and allows them in turn to activate one or more effector proteins. G protein activation is terminated when a G protein hydrolyzes bound GTP to GDP; GDP remains bound but does not activate (for review see Kaziro et al., 1991). Cells use this basic pathway - receptor → G protein → effector - to form a complex information-processing network in the plasma membrane (Fig. 1). A cell responds to selected hormones by expressing appropriate receptors, which may be highly selective for a single G protein or may activate multiple G proteins. Expression of receptor isoforms that are selective for different G proteins can generate diverse cellular signals in response to a single hormone. At the next level in the network, a G protein (some cells express six or more) may respond to several different receptors, one G protein may activate or inhibit one or more of at least a dozen effector proteins. Effectors include enzymes that generate or degrade second messengers (adenylyl cyclase, cyclic GMP phosphodiesterase, phosphoinositide-specific phospholipase C-βs), ion channels (for Na+, Ca2+, or K+), and, probably, transport proteins. As at the previous two levels, effector isoforms respond selectively to distinct G proteins. G protein networks are thus analog computers that propagate an array of cellular signals in response to stimulatory and inhibitory hormones in the milieu of the target cell.

AB - Numerous hormones of every chemical class use G protein-mediated signaling pathways to convey information from their receptors on the cell surface to the effector proteins that propagate these signals within the target cell. G proteins convey information from receptor to effector by traversing a controlled cycle of activation deactivation. When a receptor binds hormone, it promotes the binding of GTP to a select subset of the G proteins on the inner face of the plasma membrane. GTP binding activates these G proteins and allows them in turn to activate one or more effector proteins. G protein activation is terminated when a G protein hydrolyzes bound GTP to GDP; GDP remains bound but does not activate (for review see Kaziro et al., 1991). Cells use this basic pathway - receptor → G protein → effector - to form a complex information-processing network in the plasma membrane (Fig. 1). A cell responds to selected hormones by expressing appropriate receptors, which may be highly selective for a single G protein or may activate multiple G proteins. Expression of receptor isoforms that are selective for different G proteins can generate diverse cellular signals in response to a single hormone. At the next level in the network, a G protein (some cells express six or more) may respond to several different receptors, one G protein may activate or inhibit one or more of at least a dozen effector proteins. Effectors include enzymes that generate or degrade second messengers (adenylyl cyclase, cyclic GMP phosphodiesterase, phosphoinositide-specific phospholipase C-βs), ion channels (for Na+, Ca2+, or K+), and, probably, transport proteins. As at the previous two levels, effector isoforms respond selectively to distinct G proteins. G protein networks are thus analog computers that propagate an array of cellular signals in response to stimulatory and inhibitory hormones in the milieu of the target cell.

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