, Volume 11, Issue 1, pp 53–62 | Cite as

Sprouty proteins, masterminds of receptor tyrosine kinase signaling

  • Miguel A. Cabrita
  • Gerhard ChristoforiEmail author
Original paper


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-dependant. 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.


EGF Endothelial cell ERK FGF Growth factors MAPK Receptor tyrosine kinase Sprouty Spred VEGF 





Cellular homologue of Casitas B-lineage lymphoma proto-oncogene product


Epidermal growth factor


EGF receptor


Endothelial nitric oxide synthase


Extracellular signal-regulated kinase


Fibroblast growth factor


FGF receptor


Glial-derived neurotrophic factor


Growth factor receptor-bound protein 2


Human microvascular endothelial cell


Hepatocyte growth factor-regulated tyrosine kinase substrate


Human umbilical vein endothelial cell


Mitogen-activated protein kinase


MAPK and ERK kinase


Mitogen-activated protein kinase-interacting kinase 1


Platelet-derived growth factor


Protein kinase C


Phospholipase C


Protein phosphatase 2A


Raf1-binding domain


Receptor tyrosine kinase


SH2-domain-containing protein tyrosine phosphatase 2


Seven-in-Absentia Homolog 2


Smooth muscle cell


Son of Sevenless 1




Spry-related proteins with Enabled/vasodilator-stimulated phosphoprotein homology 1 domain


Spry-related domain


Vascular endothelial growth factor


VEGF receptor



The authors are grateful to Drs. Imke Albrecht, Anna Fantozzi, and Tibor Schomber for critically reading the manuscript. We apologize to all colleagues whose important work we could not cite due to space limitations. M.A.C. was initially supported by a post-doctoral fellowship from the International Agency for Research on Cancer (IARC–WHO). Research in the laboratory of the authors is supported by the Swiss National Science Foundation, Swiss Bridge Award, Krebsliga Beider Basel, Swiss Cancer League, EU-FP6 Framework programmes LYMPHANGIOGENOMICS LSHG-CT-2004-503573 and BRECOSM LSHC-CT-2004-503224, SNF-NCCR Moleculary Oncology, and Novartis Pharma Inc.


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© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  1. 1.Institute of Biochemistry and Genetics, Department of BiomedicineUniversity of BaselBaselSwitzerland

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