Biology:Sprouty protein

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Sprouty
Identifiers
SymbolSprouty
PfamPF05210
InterProIPR007875

In molecular biology, the protein Sprouty is a developmental protein involved in cell signalling. It works by inhibiting the MAPK/ERK pathway.

Function

The function of this protein has been found, in Drosophila to inhibit branching of the trachea by antagonizing the BNL-FGF pathway. Also in Drosophila it is an antagonist of EGFR-mediated signaling in the eye. Most notably, in humans, it suppresses the insulin receptor and EGFR-transduced MAPK signaling pathway, but does not inhibit MAPK activation by a constitutively active mutant Ras. Sprouty inhibits of the Ras/mitogen-activated protein kinase (MAPK) cascade, a pathway crucial for developmental processes initiated by activation of various receptor tyrosine kinases. These proteins share a conserved, C-terminal cysteine-rich region, the SPR domain. This domain has been defined as a novel cytosol to membrane translocation domain.[1][2][3][4] It has been found to be a PtdIns(4,5)P2-binding domain that targets the proteins to a cellular localization that maximizes their inhibitory potential.[2][5] It also mediates homodimer formation of these proteins.[1][5]

The SPR domain can occur in association with the WH1 domain (see INTERPRO) (located in the N-terminal part of the proteins) in the Spread proteins.

References

  1. 1.0 1.1 "Distinct requirements for the Sprouty domain for functional activity of Spred proteins". Biochem. J. 388 (Pt 2): 445–54. June 2005. doi:10.1042/BJ20041284. PMID 15683364. 
  2. 2.0 2.1 "The cysteine-rich sprouty translocation domain targets mitogen-activated protein kinase inhibitory proteins to phosphatidylinositol 4,5-bisphosphate in plasma membranes". Mol. Cell. Biol. 22 (22): 7953–66. November 2002. doi:10.1128/MCB.22.22.7953-7966.2002. PMID 12391162. 
  3. "Sprouty proteins are targeted to membrane ruffles upon growth factor receptor tyrosine kinase activation. Identification of a novel translocation domain". J. Biol. Chem. 275 (42): 32837–45. October 2000. doi:10.1074/jbc.M002156200. PMID 10887178. 
  4. "Spred is a Sprouty-related suppressor of Ras signalling". Nature 412 (6847): 647–51. August 2001. doi:10.1038/35088082. PMID 11493923. Bibcode2001Natur.412..647W. 
  5. 5.0 5.1 "Sprouty1 and Sprouty2 provide a control mechanism for the Ras/MAPK signalling pathway". Nat. Cell Biol. 4 (11): 850–8. November 2002. doi:10.1038/ncb867. PMID 12402043. 
This article incorporates text from the public domain Pfam and InterPro: IPR007875