Sprouty proteins, masterminds of receptor tyrosine kinase signaling.
Angiogenesis relies on endothelial cells properly processing signals from growth factors provided in both an autocrine and a paracrine manner. These mitogens bind to their cognate receptor tyrosine kinases (RTKs) on the cell surface, thereby activating a myriad of complex intracellular signaling pathways whose outputs include cell growth, migration, and morphogenesis. Understanding how these cascades are precisely controlled will provide insight into physiological and pathological angiogenesis. The Sprouty (Spry) family of proteins is a highly conserved group of negative feedback loop modulators of growth factor-mediated mitogen-activated protein kinase (MAPK) activation originally described in Drosophila. There are four mammalian orthologs (Spry1-4) whose modulation of RTK-induced signaling pathways is growth factor- and cell context-dependent. Endothelial cells are a group of highly differentiated cell types necessary for defining the mammalian vasculature. These cells respond to a plethora of growth factors and express all four Spry isoforms, thus highlighting the complexity that is required to form and maintain vessels in mammals. This review describes Spry functions in the context of endothelial biology and angiogenesis, and provides an update on Spry-interacting proteins and Spry mechanisms of action.
Cabrita
Miguel A
MA
Institute of Biochemistry and Genetics, Department of Biomedicine, University of Basel, Mattenstrasse 28, 4058, Basel, Switzerland.
Christofori
Gerhard
G
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism / Q000502:physiology*; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; C486055:SPRY1 protein, human; C485561:SPRY2 protein, human; C407225:SPRY3 protein, human; C499038:SPRY4 protein, human; C499037:Spry4 protein, mouse; D005346:Fibroblast Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; C118389:Spry2 protein, mouse