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Binding properties and stability of the Ras-association domain of Rap1-GTP interacting adapter molecule (RIAM).

ABSTRACT: The Rap1-GTP interacting adapter protein (RIAM) is an important protein in Rap1-mediated integrin activation. By binding to both Rap1 GTPase and talin, RIAM recruits talin to the cell membrane, thus facilitating talin-dependent integrin activation. In this article, we studied the role of the RIAM Ras-association (RA) and pleckstrin-homology (PH) domains in the interaction with Rap1. We found that the RA domain was sufficient for GTP-dependent interaction with Rap1B, and the addition of the PH domain did not change the binding affinity. We also detected GTP-independent interaction of Rap1B with the N-terminus of RIAM. In addition, we found that the PH domain stabilized the RA domain both in vitro and in cells.

SUBMITTER: Takala H

PROVIDER: S-EPMC3327698 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Binding properties and stability of the Ras-association domain of Rap1-GTP interacting adapter molecule (RIAM).

Takala Heikki H Ylänne Jari J

PloS one 20120416 4

The Rap1-GTP interacting adapter protein (RIAM) is an important protein in Rap1-mediated integrin activation. By binding to both Rap1 GTPase and talin, RIAM recruits talin to the cell membrane, thus facilitating talin-dependent integrin activation. In this article, we studied the role of the RIAM Ras-association (RA) and pleckstrin-homology (PH) domains in the interaction with Rap1. We found that the RA domain was sufficient for GTP-dependent interaction with Rap1B, and the addition of the PH do ...[more]

PMID: 22523535

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Rap1-interacting adapter molecule (RIAM) associates with the plasma membrane via a proximity detector.

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Rap1-GTP-interacting adaptor molecule (RIAM) protein controls invasion and growth of melanoma cells.

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Binding of Rap1 and Riam to Talin1 Fine-Tune β2 Integrin Activity During Leukocyte Trafficking.

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Phosphorylation of RIAM by src promotes integrin activation by unmasking the PH domain of RIAM.

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GTP-Dependent K-Ras Dimerization.

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RIAM activates integrins by linking talin to ras GTPase membrane-targeting sequences.

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SETA: a novel SH3 domain-containing adapter molecule associated with malignancy in astrocytes.

Project description:Differential display polymerase chain reaction analysis was used to compare five differentiation states of the O-2A progenitor-like cell line CG4: progenitor cells and cells at 12 h or 4 days after the induction of differentiation into oligodendrocytes or astrocytes. This led to the identification of 52 sequence tags that were expressed differentially with cellular phenotype. One sequence was upregulated during differentiation of CG4 cells and represented a novel gene that we named SETA (SH3 domain-containing gene expressed in tumorigenic astrocytes). This gene encodes an SH3 domain-containing adapter protein with sequence similarity to the CD2AP (CD2 adapter protein) and CMS (Cas ligand with multiple Src homology) genes. SETA mRNA was expressed at high levels in the developing rat brain but was barely detectable in the normal adult rat or human brain. However, SETA mRNA was found in approximately one half of the human gliomas tested, including astrocytomas grades II, III, and IV, as well as oligodendrogliomas, mixed oligoastrocytomas, and human glioma-derived cell lines. A rat glioma generated by treatment with the alkylating carcinogen ethylnitrosourea on postnatal day 1 and a derived cell line also expressed SETA mRNA. Furthermore, in an in vitro model of astrocytoma progression based on p53-/- astrocytes, expression of SETA was restricted to cells that are tumorigenic.

| S-EPMC1920697 | biostudies-other

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