The Lutheran glycoprotein: a multifunctional adhesion receptor.
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.
Duke Comprehensive Sickle Cell Center and Division of Hematology, Department of Medicine, Duke University, Durham, NC 27710, USA.
Christine E
CE
Eyler
Marilyn J
MJ
Telen
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000502:physiology; D001483:Base Sequence; D002448:Cell Adhesion / Q000502:physiology*; D004912:Erythrocytes / Q000166:cytology / Q000502:physiology; D005786:Gene Expression Regulation; D005787:Gene Frequency; D006801:Humans; D037181:Lectins, C-Type; D008188:Lutheran Blood-Group System / Q000235:genetics / Q000502:physiology*; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000502:physiology*; D008969:Molecular Sequence Data; D019038:Platelet Glycoprotein GPIb-IX Complex; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D037181:Lectins, C-Type; D008188:Lutheran Blood-Group System; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D019038:Platelet Glycoprotein GPIb-IX Complex; D000099192:CD69 Antigens; C094990:adhesion receptor