title: Galectin-3 secretion and tyrosine phosphorylation is dependent on the calpain small subunit, Calpain 4.
abstract: Cell adhesion and migration are important events that occur during embryonic development, immune surveillance, wound healing and in tumor metastasis. It is a multi-step process that involves both mechanical and biochemical signaling that results in cell protrusion, adhesion, contraction and retraction. Each of these events generates mechanical forces into the environment measured as traction forces. We have previously found that the calpain small subunit, Calpain 4, is required for normal traction forces, and that this mechanism is independent of the catalytic activities of the holoenzymes that are formed between Calpain 4 and each of the proteolytic heavy chains of Calpain 1 and 2. To define a potential mechanism for the Calpain 4 regulation of traction force, we have evaluated the levels of tyrosine phosphorylation, a hallmark of force dependent signaling within focal adhesions. Using 2D gel electrophoresis we compared tyrosine phosphorylation profiles of Calpain 4 deficient mouse embryonic fibroblasts (MEFs) to the levels in wildtype MEFs and MEF's deficient in the large catalytic subunits, Capn1 and Capn2. Of particular interest, was the identification of Galectin-3, a galactose binding protein known to interact with integrins. Galectin-3 has previously been shown to regulate cell adhesion and migration in both normal and tumor cells; however its full mechanism remains elusive. We have found that Calpain 4 is essential for the tyrosine phosphorylation of galectin-3, and its ultimate secretion from the cell, and speculate that its secretion interferes with the production of traction forces.
authors.affiliation: Department of Biological Sciences, Wayne State University, Detroit, MI 48202, USA.
authors.forename: Shalini
authors.initials: S
authors.lastname: Menon
authors.forename: Choong-Min
authors.initials: CM
authors.lastname: Kang
authors.forename: Karen A
authors.initials: KA
authors.lastname: Beningo
mesh_terms: D000818:Animals; D002154:Calpain / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology*; D022001:Focal Adhesions; D037502:Galectin 3 / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism*
chemical_list: D037502:Galectin 3; D014443:Tyrosine; D002154:Calpain; C410233:Capns1 protein, mouse