Angiogenesis

, Volume 11, Issue 1, pp 53–62

Sprouty proteins, masterminds of receptor tyrosine kinase signaling

Authors

  • Miguel A. Cabrita
    • Institute of Biochemistry and Genetics, Department of BiomedicineUniversity of Basel
    • Institute of Biochemistry and Genetics, Department of BiomedicineUniversity of Basel
Original paper

DOI: 10.1007/s10456-008-9089-1

Cite this article as:
Cabrita, M.A. & Christofori, G. Angiogenesis (2008) 11: 53. doi:10.1007/s10456-008-9089-1

Abstract

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.

Keywords

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

Abbreviations

Ang

Angiopoietin

c-Cbl

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

EGF

Epidermal growth factor

EGFR

EGF receptor

eNOS

Endothelial nitric oxide synthase

ERK

Extracellular signal-regulated kinase

FGF

Fibroblast growth factor

FGFR

FGF receptor

GDNF

Glial-derived neurotrophic factor

Grb2

Growth factor receptor-bound protein 2

HMVEC

Human microvascular endothelial cell

Hrs

Hepatocyte growth factor-regulated tyrosine kinase substrate

HUVEC

Human umbilical vein endothelial cell

MAPK

Mitogen-activated protein kinase

MEK

MAPK and ERK kinase

Mnk1

Mitogen-activated protein kinase-interacting kinase 1

PDGF

Platelet-derived growth factor

PKC

Protein kinase C

PLC

Phospholipase C

PP2A

Protein phosphatase 2A

RBD

Raf1-binding domain

RTK

Receptor tyrosine kinase

Shp2

SH2-domain-containing protein tyrosine phosphatase 2

SIAH2

Seven-in-Absentia Homolog 2

SMC

Smooth muscle cell

Sos1

Son of Sevenless 1

Spry

Sprouty

Spred

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

SPR

Spry-related domain

VEGF

Vascular endothelial growth factor

VEGFR

VEGF receptor

Copyright information

© Springer Science+Business Media B.V. 2008