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SPRY2

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Template:PBB 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 (RTK's) 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. ^ 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): 253–263. doi:10.1016/S0092-8674(00)80919-8. PMID 9458049.{{cite journal}}: CS1 maint: multiple names: authors list (link) Cite error: The named reference "pmid9458049" was defined multiple times with different content (see the help page).
  2. ^ "Entrez Gene: SPRY2 sprouty homolog 2 (Drosophila)".
  3. ^ 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 (Epub 2009). "Expression of sprouty2 inhibits B-cell proliferation and is epigenetically silenced in mouse and human B-cell lymphomas". Blood. 113 (11): 2478–2487. doi:10.1182/blood-2008-05-156943. PMC 2656273. PMID 19147787. {{cite journal}}: Check date values in: |year= (help)CS1 maint: multiple names: authors list (link) CS1 maint: year (link)
  4. ^ Lee CC, Putnam AJ, Miranti CK, Gustafson M, Wang LM, Vande Woude GF, Gao CF (2004). "Overexpression of sprouty 2 inhibits HGF/SF-mediated cell growth, invasion, migration, and cytokinesis". Oncogene. 23 (30): 5193–5202. doi:10.1038/sj.onc.1207646. PMID 15122328.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ^ Sánchez A, Setién F, Martinez N, Oliva JL, Herranz M, Fraga MF, Alaminos M, Esteller M, Rojas JM. (2008). "Epigenetic inactivation of the ERK inhibitor Spry2 in B-cell diffuse lymphomas". Oncogene. 27 (36): 4969–4972. doi:10.1038/onc.2008.129. PMID 18427547.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. ^ a b Bundschu K, Walter U, Schuh K (Epub 2006). "The VASP-Spred-Sprouty domain puzzle". J. Biol. Chem. 281 (48): 36477–36481. doi:10.1074/jbc.R600023200. PMID 16987806. {{cite journal}}: Check date values in: |year= (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) CS1 maint: year (link)
  7. ^ Wong, E S; Lim J; Low B C; Chen Q; Guy G R (February 2001). "Evidence for direct interaction between Sprouty and Cbl". J. Biol. Chem. 276 (8). United States: 5866–5875. doi:10.1074/jbc.M006945200. ISSN 0021-9258. PMID 11053437. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help)CS1 maint: unflagged free DOI (link)
  8. ^ Wong, Esther Sook Miin; Fong Chee Wai; Lim Jormay; Yusoff Permeen; Low Boon Chuan; Langdon Wallace Y; Guy Graeme R (September 2002). "Sprouty2 attenuates epidermal growth factor receptor ubiquitylation and endocytosis, and consequently enhances Ras/ERK signalling". EMBO J. 21 (18). England: 4796–4808. doi:10.1093/emboj/cdf493. ISSN 0261-4189. PMC 126289. PMID 12234920. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help)
  9. ^ Ng, Cherlyn; Jackson Rebecca A; Buschdorf Jan P; Sun Qingxiang; Guy Graeme R; Sivaraman J (March 2008). "Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates". EMBO J. 27 (5). England: 804–816. doi:10.1038/emboj.2008.18. PMC 2265755. PMID 18273061. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help)

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