Abstract
Sialomucin complex (SMC) is a high Mr glycoprotein heterodimer, originally discovered on the cell surfaces of ascites sublines of the highly metastatic 13762 rat mammary adenocarcinoma, and composed of mucin (ASGP-1) and transmembrane (ASGP-2) subunits. SMC is encoded by a single gene and synthesized as a large precursor protein which is cleaved into its subunits early in its transit to the cell surface. SMC exhibits behavior typical of both membrane and secreted mucins. In the ascites cells, it is found only in the membrane form, creating a protective barrier at the cell surface to reduce cell adhesiveness and protect the tumor cell from immune killing. Normal tissues express both the membrane formand a non-membrane form, which may be secreted by either constitutive or regulated, secretory granule mechanisms. This soluble form is proposed to contribute to multilayer mucus gels which protect epithelia, though it may also play other roles. ASGP-2 contains two EGF-like domains, one of which binds the receptor tyrosine kinase ErbB-2. Thus, SMC may be a bifunctional protein, the mucin serving a protective function and the transmembrane domain possibly playing a role in the proliferation of metastatic tumor cells or repair processes necessary for the maintenance of damaged epithelia.