The Lutheran glycoprotein: a multifunctional adhesion receptor

Abstract

The Lutheran blood group system, which comprises one of the largest families of human red blood cell (RBC) antigens, resides on two immunoglobulin superfamily (IgSF) proteins: Lutheran and basal cell adhesion molecule (B-CAM). These two glycoproteins arise via alternative splicing of mRNA from a single gene and differ in structure only in the lengths of their cytoplasmic tails. Both are expressed on RBCs as well as a variety of other cell types, and they are overexpressed on sickle RBCs (SS RBC). B-CAM/Lu is the critical receptor for SS RBC adhesion to the extracellular matrix protein laminin, an interaction thought to contribute to the pathogenesis of sickle cell-related vasoocclusive events. Recent work has also shown that B-CAM/Lu on RBCs can undergo activation as a result of adrenergic signaling pathways. The high affinity of B-CAM/Lu for laminin is also thought to contribute to various developmental processes, including organogenesis, vascular development, erythropoiesis, and smooth muscle development and organization. Interestingly, the B-CAM spliceoform seems to be overexpressed by a variety of different malignant tumors and may be involved, along with other adhesion receptor proteins, in malignant transformation and tumor metastasis. Studies of B-CAM/Lu have thus expanded from defining antigen-specific polymorphisms to investigations of processes involved in sickle cell disease, human development, and cancer biology.

Funções biológicas dos antígenos eritrocitários

“…Estudos têm demonstrado que as glicoproteínas Lu/B-CAM estão expressas em maior quantidade em diferentes tumores malignos e podem estar envolvidas, junto com outras proteínas receptoras de adesão, em metástase tumoral. 50,51 Sistema de Grupo Sanguíneo LW A glicoproteína LW (ICAM-4 e CD242) é produto do gene ICAM4, localizado no cromossomo 19, e expressa o antígeno de grupo sanguíneo LW. Essa glicoproteína possui o domínio N-terminal extracelular, com dois domínios da superfamília das imunoglobulinas, que tem sequência homó-loga à proteína da família de moléculas de adesão intercelular (ICAMs).…”

Butyrate-Mediated Genomic Changes Involved in Non-Specific Host Defenses, Matrix Remodeling and the Immune Response in the Rumen Epithelium of Cows Afflicted With Subacute Ruminal Acidosis

“…These events involve a wide variety of genes. In this study, BCAM (a receptor for matrix proteins) was elevated in addition to RAC3, which together aid in the remodelling process (Haataja et al, 2002;Eyler and Telen, 2006). It is unknown how long the early phases of remodeling occur in rumen epithelium.…”

The LG1-3 Tandem of Laminin α5 Harbors the Binding Sites of Lutheran/Basal Cell Adhesion Molecule and α3β1/α6β1 Integrins

“…Laminin-511/521 (␣5␤1␥1/␣5␤2␥1) trimers are bound by several different receptors, including integrins ␣3␤1, ␣6␤1, and ␣6␤4 (12, 13), ␣-dystroglycan (14), and Lutheran/basal cell adhesion molecule (Lu/B-CAM) (15)(16)(17). Lu is a member of the immunoglobulin superfamily and has been studied primarily in the contexts of blood group antigens and sickle cell disease (18,19). B-CAM, a splice variant of Lu, has the same NH 2 -terminal extracellular domain as Lu, but it lacks the COOH-terminal 40 amino acids of the cytoplasmic tail, which carries an Src homology 3 binding motif and potential phosphorylation sites that could be involved in intracellular signaling pathways (20).…”