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• W3024473365 abstract "Abstract GPR56, also known as ADGRG1, is a member of the adhesion G protein-coupled receptor (aGPCR) family shown to play important roles in cell adhesion, brain development, immune system function, and tumorigenesis. GPR56 is upregulated in colorectal cancer and high expression correlates with poor prognosis. Several studies have shown that GPR56 couples to the Gα 12/13 class of heterotrimeric G-proteins to promote RhoA activation. However, due to its structural complexity and lack of a high affinity receptor-specific ligand, the complete GPR56 signaling mechanism still remains largely unknown. To delineate the activation mechanism and intracellular signaling functions of GPR56, we generated a monoclonal antibody (mAb) which binds GPR56 with high affinity and specificity to the extracellular domain (ECD). We show that overexpression of GPR56 in 293T cells lead to increased phosphorylation of Src, Fak, and paxillin adhesion proteins and activation of the Gα 12/13 -RhoA-mediated serum response factor (SRF) pathway. Treatment of cells with anti-GPR56 mAb potentiated Src-Fak phosphorylation, RhoA-SRF signaling, and cell adhesion. Consistently, knockdown of GPR56 in colorectal cancer cells decreased Src-Fak pathway phosphorylation and cell adhesion. Interestingly, GPR56-mediated activation of Src-Fak phosphorylation occurred independent of RhoA, yet mAb-induced potentiation of RhoA-SRF signaling was Src-dependent. Furthermore, we show that the Serine–Threonine–Proline-rich (STP) region of the ECD of GPR56 was not essential for mAb binding, yet was required for activation of Src-Fak signaling. These data support a new ECD-dependent mechanism by which GPR56 functions to regulate cell adhesion through activation of Src-Fak signaling." @default.
• W3024473365 created "2020-05-21" @default.
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• W3024473365 date "2020-05-13" @default.
• W3024473365 modified "2023-10-17" @default.
• W3024473365 title "Anti-GPR56 monoclonal antibody potentiates GPR56-mediated Src-Fak signaling to modulate cell adhesion" @default.
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• W3024473365 doi "https://doi.org/10.1101/2020.05.11.089177" @default.
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