SPRY2

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

SPRY2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3BUM, 3OB1
Identifiers
Aliases	SPRY2, hIGAN3, sprouty RTK signaling antagonist 2
External IDs	OMIM: 602466; MGI: 1345138; HomoloGene: 4267; GeneCards: SPRY2; OMA:SPRY2 - orthologs
Gene location (Human) Chr. Chromosome 13 (human) Band 13q31.1 Start 80,335,976 bp End 80,341,126 bp
Gene location (Mouse) Chr. Chromosome 14 (mouse) Band 14 E2.3|14 56.16 cM Start 106,129,381 bp End 106,134,253 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in cartilage tissue tibial nerve right hemisphere of cerebellum left uterine tube ventricular zone pericardium parotid gland right lung right ventricle retinal pigment epithelium Top expressed in primary motor cortex blastocyst morula cingulate gyrus deep cerebellar nuclei lateral geniculate nucleus retinal pigment epithelium olfactory tubercle epiblast embryo More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein serine/threonine kinase inhibitor activity protein serine/threonine kinase activator activity protein binding protein kinase binding Cellular component cytoplasm cytosol cell projection membrane plasma membrane ruffle membrane microtubule cytoskeleton nucleus microtubule cytoskeleton Biological process cell fate commitment negative regulation of neurotrophin TRK receptor signaling pathway positive regulation of protein kinase B signaling negative regulation of epidermal growth factor receptor signaling pathway lung morphogenesis lung development bud elongation involved in lung branching negative regulation of peptidyl-threonine phosphorylation lung growth negative regulation of apoptotic process hearing positive regulation of peptidyl-serine phosphorylation negative regulation of Ras protein signal transduction multicellular organism development negative regulation of fibroblast growth factor receptor signaling pathway positive regulation of gene expression negative regulation of GTPase activity regulation of cell population proliferation regulation of signal transduction negative regulation of MAP kinase activity inner ear morphogenesis respiratory system development establishment of mitotic spindle orientation negative regulation of cell projection organization positive regulation of ERK1 and ERK2 cascade regulation of cell differentiation branching morphogenesis of an epithelial tube negative regulation of cell population proliferation positive regulation of protein serine/threonine kinase activity positive regulation of cell migration negative regulation of ERK1 and ERK2 cascade cellular response to leukemia inhibitory factor negative regulation of angiogenesis cellular response to vascular endothelial growth factor stimulus negative regulation of vascular endothelial growth factor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 10253 24064 Ensembl ENSG00000136158 ENSMUSG00000022114 UniProt O43597 Q9QXV8 RefSeq (mRNA) NM_005842 NM_001318536 NM_001318537 NM_001318538 NM_011897 RefSeq (protein) NP_001305465 NP_001305466 NP_001305467 NP_005833 NP_036027 Location (UCSC) Chr 13: 80.34 – 80.34 Mb Chr 14: 106.13 – 106.13 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

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.

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

Interactions

SPRY2 has been shown to interact with Cbl gene.

See also

• SPRED1 gene
• Neurofibromin 1
• SPRY1

Further reading

• 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.
• 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". The Journal of Biological Chemistry. 275 (42): 32837–45. doi:10.1074/jbc.M002156200. PMID 10887178.
• Glienke J, Fenten G, Seemann M, Sturz A, Thierauch KH (August 2000). "Human SPRY2 inhibits FGF2 signalling by a secreted factor". Mechanisms of Development. 96 (1): 91–9. doi:10.1016/S0925-4773(00)00378-6. PMID 10940627.
• 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.
• Hartley JL, Temple GF, Brasch MA (November 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
• Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A (March 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Research. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
• Yusoff P, Lao DH, Ong SH, Wong ES, Lim J, Lo TL, Leong HF, Fong CW, Guy GR (February 2002). "Sprouty2 inhibits the Ras/MAP kinase pathway by inhibiting the activation of Raf". The Journal of Biological Chemistry. 277 (5): 3195–201. doi:10.1074/jbc.M108368200. PMID 11698404.
• Egan JE, Hall AB, Yatsula BA, Bar-Sagi D (April 2002). "The bimodal regulation of epidermal growth factor signaling by human Sprouty proteins". Proceedings of the National Academy of Sciences of the United States of America. 99 (9): 6041–6. Bibcode:2002PNAS...99.6041E. doi:10.1073/pnas.052090899. PMC 122898. PMID 11983899.
• 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 126289. PMID 12234920.
• 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". Molecular and Cellular Biology. 22 (22): 7953–66. doi:10.1128/MCB.22.22.7953-7966.2002. PMC 134720. PMID 12391162.
• Hanafusa H, Torii S, Yasunaga T, Nishida E (November 2002). "Sprouty1 and Sprouty2 provide a control mechanism for the Ras/MAPK signalling pathway". Nature Cell Biology. 4 (11): 850–8. doi:10.1038/ncb867. PMID 12402043. S2CID 31064800.
• Yigzaw Y, Poppleton HM, Sreejayan N, Hassid A, Patel TB (January 2003). "Protein-tyrosine phosphatase-1B (PTP1B) mediates the anti-migratory actions of Sprouty". The Journal of Biological Chemistry. 278 (1): 284–8. doi:10.1074/jbc.M210359200. PMID 12414790.
• Hall AB, Jura N, DaSilva J, Jang YJ, Gong D, Bar-Sagi D (February 2003). "hSpry2 is targeted to the ubiquitin-dependent proteasome pathway by c-Cbl". Current Biology. 13 (4): 308–14. doi:10.1016/S0960-9822(03)00086-1. PMID 12593796.
• Sasaki A, Taketomi T, Kato R, Saeki K, Nonami A, Sasaki M, Kuriyama M, Saito N, Shibuya M, Yoshimura A (May 2003). "Mammalian Sprouty4 suppresses Ras-independent ERK activation by binding to Raf1". Nature Cell Biology. 5 (5): 427–32. doi:10.1038/ncb978. PMID 12717443. S2CID 33846459.
• Fong CW, Leong HF, Wong ES, Lim J, Yusoff P, Guy GR (August 2003). "Tyrosine phosphorylation of Sprouty2 enhances its interaction with c-Cbl and is crucial for its function" (PDF). The Journal of Biological Chemistry. 278 (35): 33456–64. doi:10.1074/jbc.M301317200. PMID 12815057.
• Hanafusa H, Torii S, Yasunaga T, Matsumoto K, Nishida E (May 2004). "Shp2, an SH2-containing protein-tyrosine phosphatase, positively regulates receptor tyrosine kinase signaling by dephosphorylating and inactivating the inhibitor Sprouty". The Journal of Biological Chemistry. 279 (22): 22992–5. doi:10.1074/jbc.M312498200. PMID 15031289.
• 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. S2CID 56279.
• Chi L, Zhang S, Lin Y, Prunskaite-Hyyryläinen R, Vuolteenaho R, Itäranta P, Vainio S (July 2004). "Sprouty proteins regulate ureteric branching by coordinating reciprocal epithelial Wnt11, mesenchymal Gdnf and stromal Fgf7 signalling during kidney development". Development. 131 (14): 3345–56. doi:10.1242/dev.01200. PMID 15201220. S2CID 6471981.

External links

• SPRY2 human gene location in the UCSC Genome Browser.
• SPRY2 human gene details in the UCSC Genome Browser.