The Lutheran (Lu) blood group and basal cell adhesion molecule (BCAM) antigens are both carried by 2 glycoprotein isoforms of the immunoglobulin superfamily representing receptors for the laminin alpha(5) chain. It is a transmembrane receptor with five immunoglobulin-like domains in its extracellular region , and is therefore classified as a member of the immunoglobulin (Ig) gene family. In addition to red blood cells , Lu/BCAM proteins are expressed in endothelial cells of vascular capillaries and in epithelial cells of several tissues. BCAM/LU has a wide tissue distribution with a predominant expression in the basal layer of the epithelium and the endothelium of blood vessel walls. As designated as CD239 recently , BCAM and LU share a significant sequence similarity with the CD146 (MUC18) and CD166 , and themselves are adhesion molecules that bind laminin with high affinity. Laminins are found in all basement membranes and are involved in cell differentiation , adhesion , migration , and proliferation. BCAM is upregulated following malignant transformation of some cell types in vivo and in vitro , thus being a candidate molecule involved in tumor progression. In addition , BCAM interacts with integrin in sickle red cells , and thus may potentially play a role in vaso-occlusive episodes.
Siglecs (sialic acid binding Ig-like lectins) are I-type (Ig-type) lectins belonging to the Ig superfamily. They are characterized by an N-terminal Ig-like V-type domain which mediates sialic acid binding, followed by varying numbers of Ig-like C2-type domains. Human Siglec-2, also known as B-cell antigen CD22 or B-lymphocyte cell adhesion molecule (BL-CAM), is a B-cell restricted glycoprotein that is expressed in the cytoplasm of progenitor B and pre-B cells and on the surface of mature B cells. Two distinct human Siglec-2/CD22 cDNAs that arise from differential RNA processing of the same gene have been isolated. Siglec-2/CD22 is an adhesion molecule that preferentially binds alpha 2,6- linked sialic acid on the same (cis) or adjacent (trans) cells. Interaction of CD22 with trans ligands on opposing cells was found to be favored over the binding of ligands in cis.
B-cell lymphoma-extra large (Bcl-xl) is a transmembrane molecule in the mitochondria. Bcl-xL (BCL2L1) , belongs to the Bcl-2 family. Members of the bcl-2 family encode proteins that function either to promote or to inhibit apoptosis. Antiapoptotic members such as Bcl-2 and Bcl-xL prevent PCD in response to a wide variety of stimuli to take part in cancer survival. Conversely, proapoptotic proteins, exemplified by Bax and Bak, can accelerate death and in some instances are sufficient to cause apoptosis independent of additional signals. The crystal and solution structures of a Bcl-2 family member, Bcl-xL is like this: The structures consist of two central, primarily hydrophobic α-helices, which are surrounded by amphipathic helices. A 60-residue loop connecting helices αl and α2 was found to be flexible and non-essential for anti-apoptotic activity. Bcl-xL is chareacterized as important factors in autophagy, inhibiting Beclin 1-mediated autophagy by binding to Beclin 1. In addition, Beclin 1, Bcl-2 and Bcl-xL can cooperate with Atg5 or Ca2+ to regulate both autophagy and apoptosis. Bcl-xL is also implicated in anoxia induced cell death. The pathway is initiated by the loss of function of the prosurvival Bcl-2 family members Mcl-1 and Bcl-2 / Bcl-XL, resulting in Bax- or Bak-dependent release of cytochrome c and subsequent caspase-9-dependent cell death. Thus, Bcl-xL, the well-characterized apoptosis guards, appears to be important in cell death.
The Bcr gene was orginally identified by its presence in the chimeric Bcr-Abl oncogene. The amino-terminal region of Bcr contains an oligomerization domain, a serine/threonine kinase domain, and a region that binds SH2 domains. The middle of the protein has a PH domain and a region of sequence similarity to the guanine nucleotide exchange factors for the Rho family of GTP binding proteins. The carboxy-terminal region may be involved in a GTPase activating function for the small GTP-binding protein Rac. The function of wild type Bcr in cells remains unclear. PDGF receptor may use Bcr as a downstream signaling mediator. Research studies have shown that the Bcr-Abl fusion results in production of a constitutively active tyrosine kinase, which causes chronic myelogenous leukemia (CML). Tyr177 of Bcr is phosphorylated in the Bcr-Abl fusion protein, which plays an important role in transforming the activity of Bcr-Abl). Phosphorylated Tyr177 provides a docking site for Gab2 and GRB2.
beta-Catenin, also known as CTNNB1, is a member of the armadillo family of proteins. These proteins have multiple copies of the so-called armadillo repeat domain, which is specialized for protein-protein binding. It is part of a complex of proteins that constitute adherens junctions (AJs). AJs are necessary for the creation and maintenance of epithelial cell layers by regulating cell growth and adhesion between cells. CTNNB1 also anchors the actin cytoskeleton and may be responsible for transmitting the contact inhibition signal that causes cells to stop dividing once the epithelial sheet is complete. Finally, beta-Catenin binds to the product of the APC gene, which is mutated in adenomatous polyposis of the colon. Defects in beta-Catenin can cause colorectal cancer, pilomatrixoma (PTR), medulloblastoma, and ovarian cancer. CTNNB1 is a key dowstream component of the canonical Wnt signaling pathway. In the absence of Wnt, it forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome. In the presence of Wnt ligand, beta-Catenin is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes. CTNNB1 is involved in the regulation of cell adhesion. The majority of CTNNB1 is localized to the cell membrane and is part of E-cadherin/catenin adhesion complexes which are proposed to couple cadherins to the actin cytoskeleton.
Mouse Betacellulin is a single type I membrane protein which belongs to the EGF family of cytokines. EGF family has many members including EGF, TGF-a, Amphiregulin, HB-EGF, Epiregulin, Tomoregulin and the Neuregulins. Betacellulin is characterised by a six-cysteine consensus motif that forms three intra-molecular disulfide bonds crucial for binding the ErbB receptor family. Betacellulin is expressed in several tissues and tumor cells including kidney, uterus, liver, pancreas and small intestine. Betacellulin binds and activates ErbB-1 and ErbB-4 homodimers. Betacellulin is thought to play a role in the differentiation of pancreatic beta cells.Human and mouse mature BTC protein are 80% identical at the amino acid sequence level. Betacellulin is involved in many biological processes such as stimulating gastrointestinal growth. It is proteolytically processed from a larger membrane-anchored precursor and is a potent mitogen for a wide variety of cell types.
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