Fig. 10. Model for uptake mediated by cell adhesion molecules. The model shown is for signaling pathways stimulated when monomeric ICAM-1 or anti-PECAM-1 are clustered by binding to immunoconjugates. Pharmacological inhibitors and activators are indicated by italics. Cell adhesion molecules have the capacity to bind proteins that mediate direct interactions with the actin cytoskeleton, such as -actinin (-act) and ERM proteins. On the basis of our inhibitor data and results from the literature, we propose that clustering of ICAM-1 or PECAM-1 can also stimulate PKC, Src kinase and ROCK signal transduction pathways. This could help regulate the recruitment of other cofactors, such as dynamin-2 (dyn2), to the plasma membrane. Also, ERM proteins and NHE transporters are downstream targets for phosphorylation by the Rho/ROCK pathway, which might further serve to recruit actin to sites of immunoconjugate uptake in response to ICAM-1 or PECAM-1 clustering.

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