CD69 was initially described as being restricted to recently activated lymphoid cells, but is now known to be expressed on the surface of all hematopoietically derived leukocytes. Crosslinking of CD69 generates intracellular signals in all cell lineages studied, both mouse and human, and results in a variety of celkdar end responses. Since a specific ligand has not yet been identified, a definite functional identity tor CD69 is still missing. However, as discussed here by Roberto Testi and colleagues, the broad expression of CD69 and its conserved ability to generate intracellular signals suggests a general role for the CD69 receptor in the biology of hematopoietic cells.

Human CD69 is a surface homodimer formed by the association of 28 kDa and 32 kDa chains, which are held together by disulfide bridges. Cloning and expression of the gene for human CD69 has revealed that the two chains result from the differential glycosylation of a 22.5 kDa polypeptide of 199 amino acids in length encoded by a single gene-3. These products can randomly assemble into 28-28, 28-32 and 32-32kDa dimers, although infrequent 22-22 kDa nonglycosylated dimers can also be detected 4. There is only one potential site for N-linked giycosyiation in the extracellular portion of each chain, located at amino acid position 166, suggesting a qualitative heterogeneity in chain glycosylation s. The structural and functional significance of such heterogeneity is currently unknown, Glycosylation patterns appear to be more complex in the mouse CD69 molecule, where three potential sites for N-linked glycosylation can be identified, accounting for the apparent molecular weight of 35-40kDa of each mature chain 6. Both chains appear to be constitutively phosphorylated on serine residues. Of the eight serine residues found in the intracellular portion of the human molecule (approximately 40 amino acids in length), Set18 and Set30 represent potential phosphorylation sites for casein kinase II (CKII) and protein kinase C (PKCL respectively. Constitutive phosphorylation is found in all human cells investigated, as well as mouse~ and is likely to have imgortant implications for signal generation from CD69. Primary sequence analysis indicates that CD69 is a type II integral membrane protein with a single transmembrane domain. The murine gene shows a 58% identity with the human counterpart, with the homology extending the entire length of the coding sequence. The extracellular portion of the molecule (approximately 138 amino acids in length) contains a C-type