In addition, only upon dual receptor activation (i.e. β3 integrin and TβRs) was TβR-II phosphorylated on tyrosine residues.
Moderate expression of c-FLIPL was shown to promote apoptosis only upon strong receptor stimulation or in combination with overexpression of c-FLIPS or c-FLIPR.
A more recent report described a mathematical model of CD95-induced apoptosis where c-FLIPL has a proapoptotic role only upon strong receptor stimulation or in the presence of high amounts of one of the short c-FLIP isoforms, c-FLIPS or c-FLIPR.
Moreover, studies of near full-length EGFR [ 16] indicated that the apparent Ki value for inhibition by lapatinib is increased only 1.8-fold upon receptor activation.
Recently, a single-chain antibody that specifically recognizes ligand-induced binding sites (LIBS) on GP IIb/IIIa receptors, which become exposed only upon activation by receptor-ligand binding, has been developed [81 83] The LIBS antibody has been shown to bind only to activated platelets, e.g. when adherent to damaged endothelium, and does not to bind to non-activated circulating platelets.
Because signal transduction is linked to the conformational change that occurs only upon binding, these receptors allow for detection of a specific target even within the incredibly complex media that exist within biological system.
In contrast to GPI-anchored CEACAMs, which constitutively localize to the detergent-resistant membrane fraction, CEACAM1 is only found in membrane microdomains upon receptor clustering [ 67].
The first type includes mutations affecting the transmembrane domain, whereby disulfide homodimerization of two mutant receptors induces constitutive activation of downstream signaling pathways, usually induced only upon ligand binding to the heterodimer receptor complex.
Figure 10 is a possible model of LeEix2 – AtEHD2 binding upon EIX application (we recently demonstrated that the full LeEix2 receptor binds AtEHD2 only upon EIX application [6]).
LC express Langerin/CD207 and DEC-205/CD205, albeit the latter receptor at substantial levels only upon activation.
