Abstract
Receptor tyrosine kinase (RTK) signaling is spatially and temporally regulated by a number of positive and negative regulatory mechanisms. These regulatory mechanisms control the amplitude and duration of the signals initiated at the cell surface to have a normal or aberrant biological outcome in development and disease, respectively. In the past decade, the Sprouty (Spry) family of proteins has been identified as modulators of RTK signaling in normal development and disease. This review summarizes recent advances concerning the biological activities modulated by Spry family proteins, their interactions with signaling proteins, and their involvement in cardiovascular diseases and cancer. The diversity of mechanisms in the regulation of Spry expression and activity in cell systems emphasizes the crucial role of Spry proteins in development and growth across the animal kingdom.
- Spry, Sprouty
- RTK, receptor tyrosine kinase
- FGF, fibroblast growth factor
- FGFR, FGF receptor
- EGF, epidermal growth factor
- EGFR, EGF receptor
- VEGF, vascular endothelial growth factor
- ERK1/2, extracellular signal-regulated kinases 1/2
- Cbl, Casitas b-lineage lymphoma proto-oncogene
- PtdIns(4,5)P2, phosphatidylinositol 4,5-bisphosphate
- PTP1B, protein tyrosine phosphatase 1B
- PTEN, phosphatase and tensin homolog
- Grb2, growth factor receptor-bound protein 2
- MAPK, mitogen-activated protein kinase
- Mnk1, MAPK interacting kinase 1
- DYRK1A, dual-specificity tyrosine-phosphorylated and -regulated kinase 1A
- TESK1, testicular protein kinase 1
- PP2A, protein phosphatase 2A
- SHP2, SH2-domain containing tyrosine phosphatase 2
- TKB, tyrosine kinase binding
- SIAH2, seven in absentia homolog 2
- CIN85, Cbl interacting protein of 85 kDa
- NSCLC, non–small-cell lung cancer
- aa, amino acid(s)
- TKB, tyrosine kinase binding
- xPAPC, Xenopus laevis paraxial protocadherin.
Footnotes
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This work was supported by the National Institutes of Health National Institute of General Medical Sciences [Grant GM073181].
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Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.
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ABBREVIATIONS:
- Received March 4, 2009.
- Accepted July 1, 2009.
- © 2009 The American Society for Pharmacology and Experimental Therapeutics
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Intermolecular Interactions of Sprouty Proteins and Their Implications in Development and Disease
