Molecular scaffolds regulate bidirectional crosstalk between Wnt and classical seven-transmembrane-domain receptor signaling pathways.
Signaling downstream of classical seven-transmembrane domain receptors (7TMRs) had generally been thought to recruit factors that are in large part separate from those recruited by atypical 7TMRs, such as Frizzleds (Fzs), receptors for the Wnt family of glycoproteins. Classical 7TMRs are also known as G protein-coupled receptors (GPCRs) and are mediated by signaling factors such as heterotrimeric guanine nucleotide-binding proteins (G proteins), GPCR kinases (GRKs), and beta-arrestins. Over the past few years, it has become increasingly apparent that classical and atypical 7TMRs share these factors, which are often associated with mediating classical 7TMR signaling, as well as the scaffolding proteins that were initially thought to be involved in transmitting atypical 7TMR signals. This sharing of signaling components by agonists that bind classical 7TMRs and those binding to atypical 7TMRs establishes the possibility of extensive crosstalk between these receptor classes. We discuss the evidence for, and against, crosstalk, and examine mechanisms by which this can occur.
Force
Thomas
T
The Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA. thomas.force@jefferson.edu
Woulfe
Kathleen
K
Koch
Walter J
WJ
Kerkelä
Risto
R
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000818:Animals; D019390:Arrestins / Q000502:physiology; D060466:Axin Protein; D004705:Endocytosis; D051157:Frizzled Receptors / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008954:Models, Biological; D020239:Receptor Cross-Talk / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000502:physiology*; D012097:Repressor Proteins / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D051820:TCF Transcription Factors / Q000502:physiology; D051153:Wnt Proteins / Q000737:chemistry / Q000502:physiology*; D051176:beta Catenin / Q000737:chemistry / Q000502:physiology; D000071557:beta-Arrestins
D048868:Adaptor Proteins, Signal Transducing; D019390:Arrestins; D060466:Axin Protein; D051157:Frizzled Receptors; D047908:Intracellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; D012097:Repressor Proteins; D051820:TCF Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin; D000071557:beta-Arrestins