Three proteins regulating integrin function - filamin, 14-3-3 and RIAM

摘要: Takala, Heikki Three proteins regulating integrin function – filamin, 14-3-3 and RIAM Jyvaskyla: University of Jyvaskyla, 2011, 78 p. (Jyvaskyla Studies in Biological Environmental Science ISSN 1456-9701; 232) ISBN 978-951-39-4523-7 (nid.) 978-951-39-4524-4 (PDF) Yhteenveto: Kolme integriinin toimintaa saatelevaa proteiinia filamiini, ja Diss. Integrins are transmembrane adhesion receptors important cell adhesion, migration survival. Integrin activation is regulated by cytoplasmic protein– protein interactions. Talin activates integrins binding to tails. As dozens other interact with integrins, their mutual interactions structures have be carefully regulated. This achieved, e.g., recruitment, competitive binding, alternative splicing phosphorylation. The Rap1-GTP interacting adapter molecule (RIAM) recruits talin Rap1 GTPase, thereby facilitating activation. Filamins compete for binding. expected particularly a splice variant-1 (var-1) filamin A (FLNa) that lacks segment an autoinhibitory role tail 2 phosphorylated on threonine residue upon inside-out events, which accompanied In this thesis, the structural functional properties RIAM, FLNa var-1 were studied. contains Ras-association (RA) domain followed pleckstrin homology (PH) domain. We showed RA responsible Rap1, whereas PH accounts stability protein. 41 residues. absence causes 19 unstructured unable bind ligands, but it does not seem significantly affect 21. crystal structure complex peptide reveals at atomic level how interaction dependent phosphate moiety. same phosphorylation abrogates talin. However, phosphopeptide outcompeted 14-33 , explained partially overlapping sites integrin.