Sprouty-related, EVH1 domain-containing protein 2 (SPRED2)

Sprouty-related, EVH1 domain-containing protein 2 (SPRED2) is an intracellular signaling protein that acts as a negative regulator of the Ras/MAPK signaling pathway, fundamental for growth factor-mediated cellular responses. SPRED2 contains three key domains: the N-terminal EVH1 domain (responsible for protein–protein interactions and localization), a central c-Kit binding domain (KBD, essential for ERK inhibition and membrane localization), and a C-terminal SPR domain (involved in dimerization and subcellular localization)[1]. By inhibiting ERK1/2 activation, SPRED2 controls cell proliferation, differentiation, migration, EMT, and stem cell function. Loss or downregulation of SPRED2 is associated with progression of several diseases including hepatocellular carcinoma (where it promotes stemness and drug resistance), Noonan syndrome 14 (a RASopathy), cardiovascular disease, bone growth abnormalities, diabetes, and others[1][2][3][4]. SPRED2 functions are tightly regulated spatially and temporally within cells, and its activity is essential for maintaining normal tissue homeostasis and preventing malignant transformation.

Other names

Spred-2SPRED2FLJ21897FLJ31917NS14Sprouty-related, EVH1 domain-containing protein 2Sprouty protein with EVH-1 domain 2

Not established for SPRED2-targeted drugs. For drugs affecting the Ras/MAPK pathway, mechanisms include inhibition of pathway activation and prevention of phosphorylation of downstream effectors. Downregulation of SPRED2 leads to increased stemness and resistance to certain chemotherapeutics, but no direct inhibitors or activators of SPRED2 are clinically available[2][1].