TAILIEUCHUNG - Báo cáo Y học: Human sprouty 4, a new ras antagonist on 5q31, interacts with the dual specificity kinase TESK1

TheDrosophila melanogasterprotein sprouty is induced uponfibroblast growth factor (FGF)- andepidermal growth factor (EGF)-receptor tyrosine kinase activation and acts as an inhibitor of the ras/MAP kinase pathway downstreamof these receptors. By differential displayRT-PCRof activated vs. resting umbilical artery smooth muscle cells (SMCs) we detected a new human sprouty gene, which we designated human sprouty 4 (hspry4) based on its homology with murine sprouty 4. | Eur. J. Biochem. 269 2546-2556 2002 FEBS 2002 doi Human sprouty 4 a new ras antagonist on 5q31 interacts with the dual specificity kinase TESK1 Onno C. Leeksma 1 Tanja A. E. van Achterberg 1 Yoshikazu Tsumura 4 Jiro Toshima 4 Eric Eldering 1 Wilma G. M. Kroes 2 Clemens Mellink 2 Marcel Spaargaren 3 Kensaku Mizuno 4 Hans Pannekoek1 and Carlie J. M. de Vries1 Departments of1 Biochemistry 2Clinical Genetics and 3Pathology Academic Medical Center University of Amsterdam the Netherlands 4Biological Institute Graduate School of Science Tohoku University Sendai Japan The Drosophila melanogaster protein sprouty is induced upon fibroblast growth factor FGF - and epidermal growth factor EGF -receptor tyrosine kinase activation and acts as an inhibitor of the ras MAP kinase pathway downstream of these receptors. By differential display RT-PCR of activated vs. resting umbilical artery smooth muscle cells SMCs we detected a new human sprouty gene which we designated human sprouty 4 hspry4 based on its homology with murine sprouty 4. Hspry4 is widely expressed and Northern blots indicate that different isoforms of hspry4 are induced upon cellular activation. The hspry4 gene maps to . It encodes a protein of 322 amino acids which in support of a modulating role in signal transduction contains a prototypic cysteine-rich region three potentially Src homology 3 SH3 binding proline-rich regions and a PEST sequence. This new sprouty orthologue can suppress the insulin- and EGF-receptor transduced MAP kinase signaling pathway but fails to inhibit MAP kinase activation by constitutively active V12 ras. Hspry4 appears to impair the formation of active GTP-ras and exert its activity at the level of wild-type ras or upstream thereof. In a yeast two-hybrid screen using hspry4 as bait testicular protein kinase 1 TESK1 was identified from a human fetal liver cDNA library as a partner of hspry4. The hspry4-TESK1 interaction was confirmed by .

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