Biology:SPRY2

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Sprouty homolog 2 (Drosophila), also known as SPRY2, is a protein which in humans is encoded by the SPRY2 gene.[1]

Function

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.[2]

SPRY2 is a negative feedback regulator of multiple receptor tyrosine kinases (RTKs) including receptors for fibroblast growth factor (FGF),[1] epidermal growth factor (EGF),[3] and hepatocyte growth factor (HGF).[4] Antagonization of growth factor mediated pathways, cell migration, and cellular differentiation occurs through the ERK pathway.[3] 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,[3] and in lymphoma.[5] Human spry2 expression is localized to the microtubules in unstimulated cells.[6] All sprouty isoforms inhibit the ERK pathway by themselves, but can also form heterodimers and homodimers which have enhanced inhibition.[6]

Interactions

SPRY2 has been shown to interact with Cbl gene.[7][8][9]

See also

References

  1. ↑ 1.0 1.1 "sprouty encodes a novel antagonist of FGF signaling that patterns apical branching of the Drosophila airways". Cell 92 (2): 253–63. January 1998. doi:10.1016/S0092-8674(00)80919-8. PMID 9458049. 
  2. ↑ "Entrez Gene: SPRY2 sprouty homolog 2 (Drosophila)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10253. 
  3. ↑ 3.0 3.1 3.2 "Expression of sprouty2 inhibits B-cell proliferation and is epigenetically silenced in mouse and human B-cell lymphomas". Blood 113 (11): 2478–87. March 2009. doi:10.1182/blood-2008-05-156943. PMID 19147787. 
  4. ↑ "Overexpression of sprouty 2 inhibits HGF/SF-mediated cell growth, invasion, migration, and cytokinesis". Oncogene 23 (30): 5193–202. July 2004. doi:10.1038/sj.onc.1207646. PMID 15122328. 
  5. ↑ "Epigenetic inactivation of the ERK inhibitor Spry2 in B-cell diffuse lymphomas". Oncogene 27 (36): 4969–72. August 2008. doi:10.1038/onc.2008.129. PMID 18427547. 
  6. ↑ 6.0 6.1 "The VASP-Spred-Sprouty domain puzzle". The Journal of Biological Chemistry 281 (48): 36477–81. December 2006. doi:10.1074/jbc.R600023200. PMID 16987806. 
  7. ↑ "Evidence for direct interaction between Sprouty and Cbl". The Journal of Biological Chemistry 276 (8): 5866–75. February 2001. doi:10.1074/jbc.M006945200. PMID 11053437. 
  8. ↑ "Sprouty2 attenuates epidermal growth factor receptor ubiquitylation and endocytosis, and consequently enhances Ras/ERK signalling". The EMBO Journal 21 (18): 4796–808. September 2002. doi:10.1093/emboj/cdf493. PMID 12234920. 
  9. ↑ "Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates". The EMBO Journal 27 (5): 804–16. March 2008. doi:10.1038/emboj.2008.18. PMID 18273061. 

Further reading

External links



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