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Protein SPRY2 PDB 3BUM.png
Available structures
PDB Ortholog search: PDBe RCSB
Aliases SPRY2, hIGAN3, sprouty RTK signaling antagonist 2
External IDs MGI: 1345138 HomoloGene: 4267 GeneCards: SPRY2
RNA expression pattern
PBB GE SPRY2 204011 at fs.png
More reference expression data
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 13: 80.34 – 80.34 Mb Chr 14: 105.89 – 105.9 Mb
PubMed search [1] [2]
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Sprouty homolog 2 (Drosophila), also known as SPRY2, is a protein which in humans is encoded by the SPRY2 gene.[3]


This gene encodes a protein belonging to the sprouty family. The encoded protein contains a carboxyl-terminal cysteine-rich domain essential for the inhibitory activity on receptor tyrosine kinase signaling proteins and is required for growth factor stimulated translocation of the protein to membrane ruffles. In primary dermal endothelial cells this gene is transiently upregulated in response to fibroblast growth factor two. This protein is indirectly involved in the non-cell autonomous inhibitory effect on fibroblast growth factor two signaling. The protein interacts with Cas-Br-M (murine) ectropic retroviral transforming sequence, and can function as a bimodal regulator of epidermal growth factor receptor/mitogen-activated protein kinase signaling. This protein may play a role in alveoli branching during lung development as shown by a similar mouse protein.[4]

SPRY2 is a negative feedback regulator of multiple receptor tyrosine kinases (RTK's) including receptors for fibroblast growth factor (FGF),[3] epidermal growth factor (EGF),[5] and hepatocyte growth factor (HGF).[6] Antagonization of growth factor mediated pathways, cell migration, and cellular differentiation occurs through the ERK pathway.[5] Spry2 can also enhance EGFR signaling by sequestering CBL. Spry gene expression has been reported silenced or repressed in cancer of the breast, liver, lung, prostate,[5] and in lymphoma.[7] Human spry2 expression is localized to the microtubules in unstimulated cells.[8] All sprouty isoforms inhibit the ERK pathway by themselves, but can also form heterodimers and homodimers which have enhanced inhibition.[8]


SPRY2 has been shown to interact with Cbl gene.[9][10][11]

See also[edit]


  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ a b Hacohen N, Kramer S, Sutherland D, Hiromi Y, Krasnow MA (January 1998). "sprouty encodes a novel antagonist of FGF signaling that patterns apical branching of the Drosophila airways". Cell. 92 (2): 253–63. doi:10.1016/S0092-8674(00)80919-8. PMID 9458049. 
  4. ^ "Entrez Gene: SPRY2 sprouty homolog 2 (Drosophila)". 
  5. ^ a b c Frank MJ, Dawson DW, Bensinger SJ, Hong JS, Knosp WM, Xu L, Balatoni CE, Allen EL, Shen RR, Bar-Sagi D, Martin GR, Teitell MA (March 2009). "Expression of sprouty2 inhibits B-cell proliferation and is epigenetically silenced in mouse and human B-cell lymphomas". Blood. 113 (11): 2478–87. doi:10.1182/blood-2008-05-156943. PMC 2656273Freely accessible. PMID 19147787. 
  6. ^ Lee CC, Putnam AJ, Miranti CK, Gustafson M, Wang LM, Vande Woude GF, Gao CF (July 2004). "Overexpression of sprouty 2 inhibits HGF/SF-mediated cell growth, invasion, migration, and cytokinesis". Oncogene. 23 (30): 5193–202. doi:10.1038/sj.onc.1207646. PMID 15122328. 
  7. ^ Sánchez A, Setién F, Martinez N, Oliva JL, Herranz M, Fraga MF, Alaminos M, Esteller M, Rojas JM (August 2008). "Epigenetic inactivation of the ERK inhibitor Spry2 in B-cell diffuse lymphomas". Oncogene. 27 (36): 4969–72. doi:10.1038/onc.2008.129. PMID 18427547. 
  8. ^ a b Bundschu K, Walter U, Schuh K (December 2006). "The VASP-Spred-Sprouty domain puzzle". The Journal of Biological Chemistry. 281 (48): 36477–81. doi:10.1074/jbc.R600023200. PMID 16987806. 
  9. ^ Wong ES, Lim J, Low BC, Chen Q, Guy GR (February 2001). "Evidence for direct interaction between Sprouty and Cbl". The Journal of Biological Chemistry. 276 (8): 5866–75. doi:10.1074/jbc.M006945200. PMID 11053437. 
  10. ^ Wong ES, Fong CW, Lim J, Yusoff P, Low BC, Langdon WY, Guy GR (September 2002). "Sprouty2 attenuates epidermal growth factor receptor ubiquitylation and endocytosis, and consequently enhances Ras/ERK signalling". The EMBO Journal. 21 (18): 4796–808. doi:10.1093/emboj/cdf493. PMC 126289Freely accessible. PMID 12234920. 
  11. ^ Ng C, Jackson RA, Buschdorf JP, Sun Q, Guy GR, Sivaraman J (March 2008). "Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates". The EMBO Journal. 27 (5): 804–16. doi:10.1038/emboj.2008.18. PMC 2265755Freely accessible. PMID 18273061. 

Further reading[edit]

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