doi: 10.33696/signaling.2.041.
Phosphorylation of RIAM Activates Its Adaptor Function in Mediating Integrin Signaling
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- PMID:35128538
- PMCID: PMC8813058
- DOI: 10.33696/signaling.2.041
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Phosphorylation of RIAM Activates Its Adaptor Function in Mediating Integrin Signaling
Baihao Su et al. J Cell Signal.2021.
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Abstract
Integrins are cellular receptors that regulate cell adhesion and many other cellular functions. Integrins can be activated via an "inside-out pathway" that is promoted by RAP1 GTPase. RAP1-GTP-Interacting Adaptor Molecular (RIAM) mediates integrin activation by linking RAP1 GTPase to talin, an integrin activator. RIAM's function in integrin signaling is tightly regulated. In this commentary, we review recent studies of the molecular mechanisms underlying RIAM autoinhibition via both intramolecular interaction and oligomer assembly, and the phosphorylation-dependent activation of RIAM.
Keywords: FAK; Integrin; Lamellipodin; Phosphorylation; RAP1; RIAM; SRC.
Figures
The talin-binding segment (TBS) is colored in green; inhibitory (IN) segment is in orange; coiled-coil (CC) segment is in red; poly-proline (PP) segment is in black; the Ras-associating domain (RA) is in yellow; and the pleckstrin homology domain (PH) is in cyan. The interaction of RA domain with GTP-bound RAP1 is inhibited by the IN segment, and the interaction of PH domain with phosphoinositide on the plasma membrane is inhibited by the PH domain from another RIAM molecule. Tyrosine phosphorylation sites that activate RIAM are indicated by red dots; those did not impact RIAM activity, and Ser55, are indicated by black dots.
The RA-PH module of RIAM is autoinhibited in a dimer assembly. The color scheme of RIAM is the same as Figure 1. This autoinhibitory dimer configuration is released upon phosphorylation by FAK and Src kinases. Phosphorylated tyrosines in activated RIAM are indicated by red hexagons. The two kinases activate RIAM and promotes the PM translocation of RIAM by interacting with RAP1 and the PM. RIAM in turn recruits and activates talin. Binding of talin and kindlin to the β tail of integrin activates integrin.
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