The CD34 group of monoclonal antibodies recognises CD34 (also termed CD34antigen), a 105-120kDa cell surface glycoprotein, which is selectively expressed by human myeloid and lymphoid progenitor cells, including the haemopoietic stem cell. The protein is also expressed on vascularendothelial cells. Here, it is concentrated on the surface of the inter-digitating processes, suggesting a possible involvement in cell interactionsor adhesion, by mediating the attachment of stem cells to the bone marrow extracellular matrix, or directly to stromal cells. The restricted patternof expression of CD34 in haemopoiesis suggests that it may have a significant function in the earliest stages of blood cell differentiation in the bone marrow [, ].CD34 is a phosphoprotein shown to be activated by protein kinase C (PKC) ina developmental stage-specific manner. Analysis of the human CD34 sequencereveals that the protein appears to be a type I transmembrane (TM) molecule.The predicted internal portion of the protein appears to retain basic amino acid residues adjacent to Ser residues, presenting at least two potentialtarget sites for PKC phosphorylation. In addition, there are two other consensus motifs that correspond to potential target sites for Ca+/calmodulin-dependent kinase and/or protease activated kinase I [].The protein is not strongly similar to other known proteins, but some weaksimilarities do exist: e.g., to the S+T region (a region rich in potentialO-linked carbohydrate attachment sites), the TM domain and cytoplasmic domain of cell surface proteins such as leukosialin, a major sialoglyco-protein of rat and human leukocytes; to the N-terminal glycosylated regionof CD45 (the leukocyte common antigen); and to groups of interrelatedproteins involved in cell adhesion or the regulation of complement.A homologue of human CD34 is expressed in mouse. The amino acid sequencesonly diverge significantly at their N-termini, which are predicted to be highly glycosylated and whose functions are probably modulated by carbohydrate. The observed pattern of expression of the murine CD34 geneis consistent with that of the human antigen. That CD34 is also highlyexpressed outside haematopoiesis, by vascular endothelial cells and by fibroblasts in differentiated tissue, suggests a role common to a varietyof cell types. Concentration of CD34 on the interdigitating membraneprojections of adjacent capillary endothelial cells has strengthened theidea that it functions in the control of events leading to cell-cell orcell-matrix adhesion, which role could be modulated by variation in itslevels of glycosylation. The conservation between the human and mousecysteine-rich domain in the extracellular part of the protein, and theexceptionally high conservation of the cytoplasmic domain, imply that theprotein is more than a carrier for either carbohydrate or negatively chargedterminal sialic acid residues (a role postulated for leukosialin/sialophorin).The highly conserved domain may serve to provide an internal signal of external contact with a ligand.
This family consists of several mammalian CD34 antigen proteins. The CD34 antigen is a human leukocyte membrane protein expressed specifically by lymphohematopoietic progenitor cells. CD34 is a phosphoprotein. Activation of protein kinase C (PKC) has been found to enhance CD34 phosphorylation [, ]. This family contains several eukaryotic podocalyxin proteins. Podocalyxin is a major membrane protein of the glomerular epithelium and is thought to be involved in maintenance of the architecture of the foot processes and filtration slits characteristic of this unique epithelium by virtue of its high negative charge. Podocalyxin functions as an anti-adhesin that maintains an open filtration pathway between neighbouring foot processes in the glomerular epithelium by charge repulsion [].
Podocalyxin-like protein 2 (PODXL2), also known as Endoglycan, is a ligand for the vascular selectins []. It belongs to the CD34 family, whose members contain an N-terminal acidic region appended to the sialomucin domain [].
