Glucose-regulated protein (GRP78) is an important cell surface receptor for viral invasion, cancers, and neurological disorders.

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The 78 kDa glucose-regulated protein (GRP78) is an endoplasmic reticulum (ER)-resident molecular chaperone. GRP78 is a member of the 70 kDa heat shock family of proteins involved in correcting and clearing misfolded proteins in the ER. In response to cellular stress, GRP78 escapes from the ER and moves to the plasma membrane where it (a) functions as a receptor for many ligands, and (b) behaves as an autoantigen for autoantibodies that contribute to human disease and cancer. Cell surface GRP78 (csGRP78) associates with the major histocompatibility complex class I (MHC-I), and is the port of entry for several viruses, including the predictive binding of the novel SARS-CoV-2. Furthermore, csGRP78 is found in association with partners as diverse as the teratocarcinoma-derived growth factor 1 (Cripto), the melanocortin-4 receptor (MC4R) and the DnaJ-like protein MTJ-1. CsGRP78 also serves as a receptor for a large variety of ligands including activated α2 -macroglobulin (α2 M*), plasminogen kringle 5 (K5), microplasminogen, the voltage-dependent anion channel (VDAC), tissue factor (TF), and the prostate apoptosis response-4 protein (Par-4). In this review, we discuss the mechanisms involved in the translocation of GRP78 from the ER to the cell surface, and the role of secreted GRP78 and its autoantibodies in cancer and neurological disorders.





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Gonzalez-Gronow, Mario, Udhayakumar Gopal, Richard C Austin and Salvatore V Pizzo (2021). Glucose-regulated protein (GRP78) is an important cell surface receptor for viral invasion, cancers, and neurological disorders. IUBMB life, 73(6). pp. 843–854. 10.1002/iub.2502 Retrieved from

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Mario Gonzalez-Gronow

Associate Professor Emeritus of Pathology

I am primarily involved in studies of the regulation of the plasminogen (Pg) activation system in rheumatoid human synovial fibroblasts relative to endothelial cells, hepatocytes and monocytes. We have found that streptococcal antigens like streptokinase (SK) are able to mimic binding properties of human fibronectin (FN) and thereby have the potential to affect processes on the cell surface involving FN interaction with their normal receptors. Rheumatoid arthritis (RA) in humans is a disease characterized by a chronic autoimmune related inflammatory process focused in the joints leading to a vast destruction of synovial tissue and bone. We have found a correlation between the stage of the disease and the titer of anti-SK antibodies cross-reacting with FN. In addition, we also found that the Pg receptor in RA human synovial fibroblasts has a composition different from that found in normal synovial fibroblasts. We identified the protein components of both normal and RA synovial fibroblasts. These findings led us to postulate a new mechanism which explains the molecular basis for the upregulation of Pg activity on the surface of the rheumatoid inflammed synovium. I am also involved in the study of Pg receptors in prostate cancer cells. I found that the voltage-dependent anion channel (VDAC1) along with the chaperone protein glucose-regulated protein of 78 kDa serve as receptors for Pg. Furthermore, we identified the binding site for alpha-2-macroglobulin in GRP78. This site is the target of autoimmunity in prostate cancer patients who show elevated titers of anti-GRP78 autoantibodies which stimulate tumor cell proliferation. We are presently studying the mechanism by which these autoantibodies protect the tumor cells from apoptosis.

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