SPRED1

The human SPRED1 gene is located at 15q14 and has seven exons. The encoded SPRED protein belongs to the Sprouty-related protein family and consists of three domains: EVH1 (N-terminal Enabled/VASP homology1), SPR (Sprouty-related) and KBD (C-Kit binding domain). The EVH1 domain is a binding unit of several proteins associated with actin that binds to the proline-rich (Pro)-rich motif FPPPP and is involved in the assembly mechanism of actin during cytoskeletal remodeling. The SPR domain contains approximately 110 amino acids, which are rich in cysteine (Cys). The SPR domain is associated with SPRED1 membrane localization, ie, SPRED1 is localized to the plasma membrane through the SPR domain, while the CRED-deficient SPRED1 is localized to the cytoplasm. KBD is a C-Kit binding domain consisting of approximately 50 amino acid residues, which is essential for phosphorylation of SPRED1, and its presence allows SPRED1 to exert its inhibitory effect more fully. Inactivation of SPRED1 gene activates Ras-MAPK and RhoA cell signaling pathways, thereby prolonging proliferative survival and angiogenesis in acute myeloid leukemia (AML) cells. Therefore, SPRED1 may play an important role in the pathophysiological process of acute leukemia as a novel tumor suppressor gene.