Tiam1

TIAM1 is the protein product of the human TIAM1 gene and a member of the Dbl family of guanine nucleotide exchange factors (GEFs). It functions as a Rac1-specific GEF, promoting the exchange of GDP for GTP on Rac1 and thereby triggering actin cytoskeleton remodeling, lamellipodia formation, and cell migration. The protein contains a Dbl homology (DH) domain and a pleckstrin homology (PH) domain that are essential for its catalytic activity and membrane localization, as well as other regions that mediate regulatory interactions.

TIAM1 was originally identified as a factor associated with invasion and metastasis in T-cell lymphomas, which led to the name T-lymphoma invasion and metastasis-inducing factor 1. Beyond oncology, TIAM1 participates in neuronal development and synaptic plasticity, where Rac1 signaling influences neurite outgrowth and spine morphology. Its activity is regulated by upstream signaling pathways, including receptor tyrosine kinases and integrins, and by intramolecular interactions and post-translational modifications. Binding of phosphoinositides to the PH domain helps recruit TIAM1 to membranes and activates its GEF function.

Expression of TIAM1 is broad, with higher levels in brain and immune-related tissues, and alternative splicing generates multiple isoforms with distinct regulatory properties and localization. In cancer, dysregulation of TIAM1 can contribute to enhanced migratory and invasive behavior in certain contexts, reflecting its role in Rac signaling networks. TIAM1 has related family members, such as TIAM2, which participate in similar pathways and coordinate Rac-mediated processes.