Integrin beta-2 subunit <p>Integrins are the major metazoan receptors for cell adhesion to extracellular matrix proteins and, in vertebrates, also play important roles in certain cell-cell adhesions, make transmembrane connections to the cytoskeleton and activate many intracellular signalling pathways [<cite idref="PUB00009789"/>, <cite idref="PUB00035000"/>]. The integrin receptors are composed of alpha and beta subunit heterodimers. Each subunit crosses the membrane once, with most of the polypeptide residing in the extracellular space, and has two short cytoplasmic domains. Some members of this family have EGF repeats at the C terminus and also have a vWA domain inserted within the integrin domain at the N terminus.</p><p> Most integrins recognise relatively short peptide motifs, and in general require an acidic amino acid to be present. Ligand specificity depends upon both the alpha and beta subunits [<cite idref="PUB00035002"/>]. There are at least 18 types of alpha and 8 types of beta subunits recognised in humans [<cite idref="PUB00015915"/>]. Each alpha subunit tends to associate only with one type of beta subunit, but there are exceptions to this rule [<cite idref="PUB00015985"/>]. Each association of alpha and beta subunits has its own binding specificity and signalling properties. Many integrins require activation on the cell surface before they can bind ligands. Integrins frequently intercommunicate, and binding at one integrin receptor activate or inhibit another.</p><p> The structure of unliganded alphaV beta3 showed the molecule to be folded, with the head bent over towards the C termini of the legs which would normally be inserted into the membrane [<cite idref="PUB00035001"/>]. The head comprises a beta propeller domain at the end terminus of the alphaV subunit and an I/A domain inserted into a loop on the top of the hybrid domain in the beta subunit. The I/A domain consists of a Rossman fold with a core of beta parallel sheets surrounded by amphipathic alpha helices. </p><p>Integrin Beta-2 is also referred to as ITGB2 and is known to interact with three different alpha integrin chains: ITGAL, ITGAM and ITGAX. These three integrin heterodimers are associated with leukocyte adhesion deficiency (LAD), which is characterised by recurrent bacterial infections. LFA-1 (ITGB2/ITGAL) is one of the most well studied of these integrins. Engagement of LFA-1 results in increased AP-1 dependent gene expression, which is mediated by the nuclear translocation of JAB1 [<cite idref="PUB00035005"/>]. The ligand for LFA-1 is JAM-1, a member of the endothelial immunoglobulin superfamily. JAM-1 contributes to LFA-1 dependent transendothelial migration of leukocytes and LFA-1 mediated arrest of T cells [<cite idref="PUB00035006"/>]. Studies of marginal zone (MZ) B cells also showed that LFA-1, together with alpha4beta1, is required for localisation of those cells in the splenic MZ and that these integrins are necessary for lymphoid tissue compartmentalization [<cite idref="PUB00035007"/>].</p>