Disease relevance of SPRY4

• Human SPRY4 mRNA was expressed in embryonic stem (ES) cells, brain, pancreatic islet, colon cancer, head and neck tumor, melanoma, and pancreatic cancer [1].

High impact information on SPRY4

• This PXXPXR motif binds directly to the N-terminal Src homology domain 3 of Grb2, and when added onto the C terminus of Spry4 the resultant chimera inhibits the Ras/ERK pathway [2].
• Homology analysis further showed that the core promoter region of the hSpry4 gene exhibits significant similarity to the 5'-flanking region of the mouse gene [3].
• Transient transfection using luciferase reporter gene constructs with progressive deletions of the hSpry4 5'-flanking region revealed that the core promoter activity is located within the proximal 0.4-kb region, whereas the minimal ERK-inducible promoter activity is between -69 and -31 [3].
• The hSpry4 gene spans > 14 kb and is organized in three exons and two introns [3].
• FGF18, FGF20 and SPRY4 are potent targets of the canonical WNT signaling pathway in the gastrointestinal tract [4].

Biological context of SPRY4

• Human, chimpanzee, rat and mouse SPRY4 orthologs, consisting of three exons, were well conserved [1].
• Chimpanzee SPRY4 gene was identified within NW_107083.1 genome sequence [1].
• SPRY4 is the pharmacogenomics target in the fields of oncology and regenerative medicine [1].
• SPRY4-FGF1 locus at human chromosome 5q31.3 and FGF2-NUDT6-SPATA5-SPRY1 locus at human chromosome 4q27-q28.1 were paralogous regions within the human genome [1].
• Because double TCF/LEF-binding sites were identified within the 5'-promoter region of human SPRY4 gene, comparative genomics analyses on SPRY4 orthologs were further performed [1].

Anatomical context of SPRY4

• Epigenetic silencing and loss-of-function mutations of SPRY4 gene in progenitor cells could lead to carcinogenesis [1].
• Expression of Spry4 in cultured cells suppressed integrin-mediated cell spreading, and TESK1 reversed the inhibitory effect of Spry4 on cell spreading [5].

Associations of SPRY4 with chemical compounds

• Furthermore, Spry4 suppressed integrin- and TESK1-mediated cofilin phosphorylation during the spreading of cells on laminin [5].
• In the present study, we show that Spry4 inhibits the kinase activity of TESK1 by binding to it through the C-terminal cysteine-rich region [5].

Other interactions of SPRY4

• We previously showed that TESK1 interacts with Sprouty-4 (referred to as Spry4), an inhibitor of growth factor-induced Ras/MAP (mitogen-activated protein) kinase signalling, but the functional role of this interaction has remained unknown [5].

Analytical, diagnostic and therapeutic context of SPRY4

• The human sprouty 4 (SPRY4) gene was localized to chromosome band 5q32 approximately 33 by screening the Stanford radiation hybrid G3 panel using a SPRY4-specific primer pair for PCR [6].

References