GPCRs signaling directly through Src-family kinases.
A wide range of extracellular signals are transduced by G protein-coupled receptors (GPCRs). When activated by ligands, GPCRs can activate associated heterotrimeric guanine nucleotide-binding proteins (G proteins), which in turn act on various effectors. Increasing evidence indicates that GPCRs also signal independently of heterotrimeric G proteins. Several GPCRs directly interact with Src-family kinases. Here, we discuss the evidence for direct interaction and activation of Src-family kinases by GPCRs and data that suggest that agonist dosage provides a mechanism by which GPCRs can switch between G protein-dependent and G protein-independent signaling.
McGarrigle
Deirdre
D
Department of Physiology, Cornell University Weill Medical College, New York, NY 10021, USA.
Huang
Xin-Yun
XY
D008958:Models, Molecular; D011487:Protein Conformation; D021122:Protein Subunits / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058473:Receptors, Purinergic P2Y2; D015398:Signal Transduction / Q000502:physiology*; D019061:src-Family Kinases / Q000378:metabolism*
D021122:Protein Subunits; D011943:Receptors, Adrenergic, beta; D043562:Receptors, G-Protein-Coupled; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2; D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases