A functional interaction between sprouty proteins and caveolin-1.
Growth factor-mediated signal transduction cascades can be regulated spatio-temporally by signaling modulators, such as Sprouty proteins. The four mammalian Sprouty family members are palmitoylated phosphoproteins that can attenuate or potentiate numerous growth factor-induced signaling pathways. Previously, we have shown that Sprouty-1 and Sprouty-2 associate with Caveolin-1, the major structural protein of caveolae. Like Sprouty, Caveolin-1 inhibits growth factor-induced mitogen-activated protein kinase activation. Here, we demonstrate that all four mammalian Sprouty family members physically interact with Caveolin-1. The C terminus of Caveolin-1 is the major Sprouty-binding site, whereas Sprouty binds Caveolin-1 via its conserved C-terminal domain. A single point mutation in this domain results in loss of Caveolin-1 interaction. Moreover, we demonstrate that the various Sprouty isoforms differ dramatically in their cooperation with Caveolin-1-mediated inhibition of mitogen-activated protein kinase activation and that such cooperation is also highly dependent on the type of growth factor investigated and on cell density. Together, the data suggest that the Sprouty/Caveolin-1 interaction modulates signaling in a growth factor- and Sprouty isoform-specific manner.
Cabrita
Miguel A
MA
Institute of Biochemistry and Genetics, Department of Clinical-Biological Sciences, Center of Biomedicine, University of Basel, Mattenstrasse 28, 4058 Basel, Switzerland.
Jäggi
Fabienne
F
Widjaja
Sandra P
SP
Christofori
Gerhard
G
D000818:Animals; D019556:COS Cells; D051242:Caveolin 1 / Q000378:metabolism / Q000502:physiology*; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D010750:Phosphoproteins / Q000502:physiology*; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D015398:Signal Transduction
D051242:Caveolin 1; D008565:Membrane Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; C486055:SPRY1 protein, human; D049452:Green Fluorescent Proteins