Role of SPRY4 in health and disease

Abstract

SPRY4 is a protein encoding gene that belongs to the Spry family. It inhibits the mitogen-activated protein kinase (MAPK) signaling pathway and plays a role in various biological functions under normal and pathological conditions. The SPRY4 protein has a specific structure and interacts with other molecules to regulate cellular behavior. It serves as a negative feedback inhibitor of the receptor protein tyrosine kinases (RTK) signaling pathway and interferes with cell proliferation and migration. SPRY4 also influences inflammation, oxidative stress, and cell apoptosis. In different types of tumors, SPRY4 can act as a tumor suppressor or an oncogene. Its dysregulation is associated with the development and progression of various cancers, including colorectal cancer, glioblastoma, hepatocellular carcinoma, perihilar cholangiocarcinoma, gastric cancer, breast cancer, and lung cancer. SPRY4 is also involved in organ development and is associated with ischemic diseases. Further research is ongoing to understand the expression and function of SPRY4 in specific tumor microenvironments and its potential as a therapeutic target.

Keywords: SPRY4; apoptosis; cancer; development; metastasis; oxidative stress; proliferation; tumor suppressor.

Figure 1

Blue region: C-terminal region rich in cysteine ​​residues, which contains a domain that binds to Raf1 (Raf1 binding domain, RBD, black region);Yellow region: Amino-terminal tyrosine residue; Red region: PEST sequence.

Figure 2

RNA and protein expression of SPRY4 proteins. (A) RNA expression of SPRY4 across tissues from The Genotype Tissue Expression (GTEX) Project (https://www.gtexportal.org/home). (B) Protein expression of SPRY4 across tissues from The Human Protein Atlas (https://www.proteinatlas.org).

Figure 3

The SPRY4 protein serves as a negative feedback inhibitor of RTK signaling SPRY4 binds to free sos1 or the GRB2-SOS1 complex, thereby disrupting the interaction between GRB2 and SOS1, thereby inhibiting FGF-induced ERK activation. SPRY4 may impair the formation of active GTP-ras and exert its inhibitory effects at the level of Ras or its upstream components. The CR domain of the SPRY4 protein binds to PIP2, which effectively shields it from PLCγ, thereby inhibiting the hydrolysis of PIP2 (https://www.figdraw.com).