The adaptor molecule RIAM integrates signaling events critical for integrin-mediated control of immune function and cancer progression

Lymphocyte activation requires adhesion to antigen-presenting cells. This is a critical event linking innate and adaptive immunity. Lymphocyte adhesion is accomplished through LFA-1, which must be activated by a process referred to as inside-out integrin signaling. Among the few signaling molecules...

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Bibliographic Details
Published in:Science signaling 2017-08, Vol.10 (493)
Main Authors: Patsoukis, Nikolaos, Bardhan, Kankana, Weaver, Jessica D, Sari, Duygu, Torres-Gomez, Alvaro, Li, Lequn, Strauss, Laura, Lafuente, Esther M, Boussiotis, Vassiliki A
Format: Article
Language:English
Subjects:
Actin
Adaptive immunity
Adaptor Proteins, Signal Transducing - immunology
Adaptor Proteins, Signal Transducing - metabolism
Adhesion
Animals
Antigen-presenting cells
Cancer
Cell activation
Cell adhesion
Cell adhesion & migration
Cytoskeleton
Gloss
Guanosine
Guanosine triphosphatases
Homology
Humans
Immune response
Immune system
Immunity
Integrins
Integrins - immunology
Integrins - metabolism
Leukocyte migration
LFA-1 antigen
Lymphocyte Activation
Lymphocytes
Lymphocytes T
Membrane Proteins - immunology
Membrane Proteins - metabolism
Molecular chains
Neoplasms - immunology
Neoplasms - metabolism
Neoplasms - pathology
Pleckstrin
Proline
Proteins
Rap1 protein
Relocation
Signal Transduction
Signaling
Talin
Therapeutic applications
Triphosphatase
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Summary:Lymphocyte activation requires adhesion to antigen-presenting cells. This is a critical event linking innate and adaptive immunity. Lymphocyte adhesion is accomplished through LFA-1, which must be activated by a process referred to as inside-out integrin signaling. Among the few signaling molecules that have been implicated in inside-out integrin activation in hematopoietic cells are the small guanosine triphosphatase (GTPase) Rap1 and its downstream effector Rap1-interacting molecule (RIAM), a multidomain protein that defined the Mig10-RIAM-lamellipodin (MRL) class of adaptor molecules. Through its various domains, RIAM is a critical node of signal integration for activation of T cells, recruits monomeric and polymerized actin to drive actin remodeling and cytoskeletal reorganization, and promotes inside-out integrin signaling in T cells. As a regulator of inside-out integrin activation, RIAM affects multiple functions of innate and adaptive immunity. The effects of RIAM on cytoskeletal reorganization and integrin activation have implications in cell migration and trafficking of cancer cells. We provide an overview of the structure and interactions of RIAM, and we discuss the implications of RIAM functions in innate and adaptive immunity and cancer.
ISSN:1945-0877
1937-9145
DOI:10.1126/scisignal.aam8298