Sprouty protein
| Sprouty | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | Sprouty | ||||||||
| Pfam | PF05210 | ||||||||
| InterPro | IPR007875 | ||||||||
| |||||||||
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
- ^ a b King JA, Straffon AF, D'Abaco GM, Poon CL, I ST, Smith CM, Buchert M, Corcoran NM, Hall NE, Callus BA, Sarcevic B, Martin D, Lock P, Hovens CM (June 2005). "Distinct requirements for the Sprouty domain for functional activity of Spred proteins". Biochem. J. 388 (Pt 2): 445–54. doi:10.1042/BJ20041284. PMC 1138951. PMID 15683364.
- ^ a b Lim J, Yusoff P, Wong ES, Chandramouli S, Lao DH, Fong CW, Guy GR (November 2002). "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. doi:10.1128/MCB.22.22.7953-7966.2002. PMC 134720. PMID 12391162.
- ^ Lim J, Wong ES, Ong SH, Yusoff P, Low BC, Guy GR (October 2000). "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. doi:10.1074/jbc.M002156200. PMID 10887178.
- ^ Wakioka T, Sasaki A, Kato R, Shouda T, Matsumoto A, Miyoshi K, Tsuneoka M, Komiya S, Baron R, Yoshimura A (August 2001). "Spred is a Sprouty-related suppressor of Ras signalling". Nature. 412 (6847): 647–51. Bibcode:2001Natur.412..647W. doi:10.1038/35088082. PMID 11493923. S2CID 4345140.
- ^ a b Hanafusa H, Torii S, Yasunaga T, Nishida E (November 2002). "Sprouty1 and Sprouty2 provide a control mechanism for the Ras/MAPK signalling pathway". Nat. Cell Biol. 4 (11): 850–8. doi:10.1038/ncb867. PMID 12402043. S2CID 31064800.