Epidermal growth factor‐binding protein activates soluble and receptor‐bound single chain urokinase‐type plasminogen activator

FEBS Letters

Wolf, Beni B.²  Brown, Morry D.¹ 

[1] Departments of Pathology and Biochemistry, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA;Department of Internal Medicine, University of California at San Diego, San Diego, CA 92103, USA

关键词: Urokinase-type plasminogen activator;    Urokinase-type plasminogen activator receptor;    Epidermal growth factor binding protein;    Epidermal growth factor;    EGF;    epidermal growth factor;    EGF-BP;    EGF-binding protein;    NGF-γ;    nerve growth factor-γ;    scu-PA;    single chain urokinase type plasminogen activator;    tcu-PA;    two chain urokinase type plasminogen activator;    uPAR;    urokinase type plasminogen activator receptor;    PPACK;    d-phenylalanyl-l-prolyl-arginine chloromethyl ketone;    S-2444;    hydrochloride;    S-2251;    dihydrochloride;    PMA;    phorbol 12-myristate 13-acetate;    PNPGB;    p-nitrophenyl p′-guanidinobenzoate hydrochloride;    EGR-AMC;    glutamyl-glycyl-arginine-7-amino-4-methyl coumarin;    S.E.M.;    standard error of the mean;   

DOI  :  10.1016/0014-5793(95)01234-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Epidermal growth factor-binding protein (EGF-BP) is a serine proteinase that reversibly associates with epidermal growth factor (EGF). We analyzed the reaction of EGF-BP with urokinase type plasminogen activator (u-PA), a serine proteinase that promotes pericellular proteolysis and cellular migration. EGF-BP cleaved single chain u-PA (scu-PA) between Lys¹⁵⁸ and Ile¹⁵⁹, converting the zymogen into enzymatically active two-chain u-PA (tcu-PA), as shown by SDS-PAGE, N-terminal sequence analysis, and enzymatic assay. The k _cat and K _m of the activation reaction were (5.6 ± 0.6) × 10⁻² s ⁻¹ and 2,0 ± 0.3 μM, yielding a catalytic efficiency of 2.8 × 10⁴ M⁻¹. EGF-BP also activated scu-PA bound to receptors on U937 monocytes as demonstrated by the generation of amidase activity against a tcu-PA-specific fluorogenic substrate. By activating scu-PA, EGF-BP may initiate u-PA-dependent cell surface proteolysis and therefore enhance EGF activities that require cellular migration and/or tissue remodeling.

【 授权许可】

Unknown