RalGDS

RalGDS, or Ral guanine nucleotide dissociation stimulator, is a signaling protein that functions as a guanine nucleotide exchange factor (GEF) for the small GTPases RalA and RalB. In humans, it is encoded by the RALGDS gene. As a Ras effector, RalGDS binds to Ras when Ras is in its GTP-bound active state and transfers this signal to the Ral pathway, promoting GDP-GTP exchange on RalA and RalB.

Structurally, RalGDS contains a Ras-binding domain that mediates interaction with activated Ras. Upon binding Ras-GTP, RalGDS facilitates the activation of RalA and RalB, which then engage downstream effectors involved in various cellular processes. Active Ral GTPases regulate vesicle trafficking, cytoskeletal organization, and gene expression, in part through interactions with components of the exocyst complex and other effector pathways.

Biological role and significance are tied to its position in the Ras signaling network. RalGDS helps translate upstream signals into changes in cell shape, movement, secretion, and transcriptional programs. In some contexts, alterations in Ras-Ral signaling, including the activity of RalGDS, have been studied in development and oncogenesis, where they can influence cellular transformation and tumor progression.

Genomically, RALGDS is conserved in vertebrates and can produce multiple transcript variants via alternative splicing, yielding distinct isoforms with shared core domains. Related proteins, such as RALGDS-like family members, participate in related signaling networks and provide functional diversity within the Ral GEF system.