Characterization of GPR56 protein and its suppressed expression in human pancreatic cancer cells.
GPR56 is an atypical G protein-coupled receptor (GPCR) with an unusually large N-terminal extracellular region, which contains a long Ser/Thr-rich region forming a mucin-like stalk and due to this feature, GPR56 is thought to be an adhesion GPCR. Recent studies demonstrate that GPR56 plays a role in brain development and tumorigenesis. Here, we report that human GPR56 undergoes GPS (GPCR proteolytic site)-mediated protein cleavage to generate its extracellular domain as an N-terminal fragment (GPR56-N). We also show that GPR56-N is highly glycosylated with N-linked carbohydrate chains. Mouse Gpr56 is ubiquitously expressed in various tissues, with high levels in kidney and pancreas. GPR56 mRNA is detected in diverse human cancer cells including pancreatic cancer cells PANC-1, Capan-1, and MiaCaPa-2. Interestingly, GPR56 protein is either negligible or undetectable in these pancreatic cancer cells, despite the fact that high levels of GPR56 mRNA are observed. Moreover, we have found that protein levels of GPR56 in pancreatic cancer cells were not affected when cells were treated with a proteasome inhibitor MG132. Taken together, these results define the biochemical properties of GPR56 protein, and suggest that the expression of GPR56 protein is suppressed in human pancreatic cancer cells.
Huang
Yue
Y
Biomedical Science Graduate Program, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25704, USA.
Fan
Jun
J
Yang
Jing
J
Zhu
Guo-Zhang
GZ
D000818:Animals; D002241:Carbohydrates; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
C118925:ADGRG1 protein, human; D002241:Carbohydrates; D006023:Glycoproteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled