Cytoskeletal restraints regulate homotypic ALCAM-mediated adhesion through PKCalpha independently of Rho-like GTPases

Aukje W Zimmerman, Judith M D T Nelissen, Sjenet E van Emst-de Vries, Peter H G M Willems, Frank de Lange, John G Collard, Frank N van Leeuwen, Carl G Figdor

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

Samenvatting

The activated leukocyte cell adhesion molecule (ALCAM) is dynamically regulated by the actin cytoskeleton. In this study we explored the molecular mechanisms and signaling pathways underlying the cytoskeletal restraints of this homotypic adhesion molecule. We observed that ALCAM-mediated adhesion induced by cytoskeleton-disrupting agents is accompanied by activation of the small GTPases RhoA, Rac1 and Cdc42. Interestingly, unlike adhesion mediated by integrins or cadherins, ALCAM-mediated adhesion appears to be independent of Rho-like GTPase activity. By contrast, we demonstrated that protein kinase C (PKC) plays a major role in ALCAM-mediated adhesion. PKC inhibition by chelerythrine chloride and myristoylated PKC pseudosubstrate, as well as PKC downregulation by PMA strongly reduce cytoskeleton-dependent ALCAM-mediated adhesion. Since serine and threonine residues are dispensable for ALCAM-mediated adhesion and ALCAM is not phosphorylated, we can rule out that ALCAM itself is a direct PKC substrate. We conclude that PKCalpha plays a dominant role in cytoskeleton-dependent avidity modulation of ALCAM.

Originele taal-2Engels
Pagina's (van-tot)2841-52
Aantal pagina's12
TijdschriftJournal of cell science
Volume117
Nummer van het tijdschriftPt 13
DOI's
StatusGepubliceerd - 1 jun. 2004
Extern gepubliceerdJa

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