Tyrosine-phosphorylated galectin-3 protein is resistant to prostate-specific antigen (PSA) cleavage.
Galectin-3 is a chimeric carbohydrate-binding protein, which interacts with cell surface carbohydrate-containing molecules and extracellular matrix glycoproteins and has been implicated in various biological processes such as cell growth, angiogenesis, motility, and metastasis. It is expressed in a wide range of tumor cells and is associated with tumor progression. The functions of galectin-3 are dependent on its localization and post-translational modifications such as cleavage and phosphorylation. Recently, we showed that galectin-3 Tyr-107 is phosphorylated by c-Abl; concomitantly, it was also shown that galectin-3 can be cleaved at this site by prostate-specific antigen (PSA), a chymotrypsin-like serine protease, after Tyr-107, resulting in loss of galectin-3 multivalency while preserving its carbohydrate binding activity. Galectin-3 is largely a monomer in solution but may form a homodimer by self-association through its carbohydrate recognition domain, whereas, in the presence of a ligand, galectin-3 polymerizes up to pentamers utilizing its N-terminal domain. Oligomerization is a unique feature of secreted galectin-3, which allows its function by forming ordered galectin-glycan structures, i.e. lattices, on the cell surface or through direct engagement of specific cell surface glycoconjugates by traditional ligand-receptor binding. We questioned whether Tyr-107 phosphorylation by c-Abl affects galectin-3 cleavage by PSA. The data suggest a role for galectin-3 in prostate cells associated with increased activity of c-Abl kinase and loss of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) activity. In addition, the ratio of phosphorylated/dephosphorylated galectin-3 might be used as a complementary value to that of PSA for prognosis of prostate cancer and a novel therapeutic target for the treatment of prostate cancer.
Karmanos Cancer Institute, Wayne State University, Detroit, Michigan 48201, USA. balanv@karmanos.org
Vitaly
V
Balan
Pratima
P
Nangia-Makker
Dhong Hyo
DH
Kho
Yi
Y
Wang
Avraham
A
Raz
D045744:Cell Line, Tumor; D002633:Chemotaxis; D005110:Extracellular Space / Q000378:metabolism; D037502:Galectin 3 / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D009389:Neovascularization, Pathologic / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D011487:Protein Conformation; D059748:Proteolysis; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*
D037502:Galectin 3; D014443:Tyrosine; D016315:Proto-Oncogene Proteins c-abl; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; D017430:Prostate-Specific Antigen