Disease relevance of Tiam2

• Furthermore, experiments using a dominant-negative form demonstrate that STEF/Tiam1 mediate extracellular laminin signals to activate Rac1, promoting neurite growth in N1E-115 neuroblastoma cells [1].

High impact information on Tiam2

• Suppression of endogenous STEF and Tiam1 activities in N1E-115 cells by ectopically expressed PHnTSS STEF resulted in inhibition of neurite outgrowth in serum-starved conditions, which usually induce neurite formation [2].
• Here, we characterize the molecular nature of STEF and its involvement in neurite growth [2].
• Here we report the identification of a novel guanine nucleotide exchange factor for Rac1, STEF, which is related in overall amino acid sequence and modular structure to mouse Tiam1 and Drosophila SIF proteins [3].
• The stef transcript was observed in restricted parts of mice, including cartilaginous tissues and the cortical plate of the central nervous system during embryogenesis [3].
• Roles of STEF/Tiam1, guanine nucleotide exchange factors for Rac1, in regulation of growth cone morphology [1].

Biological context of Tiam2

• Thus, stef gene expression appears to correspond to neuronal morphological changes [4].

Anatomical context of Tiam2

• In the cerebral cortex, stef transcripts were detected in migrating cells in the intermediate zone as well as neurons in the cortical plate [4].
• In situ hybridization revealed that the stef gene was expressed in a stage- and region-specific manner in the mouse brain; it was expressed during certain developmental stages in the cerebral cortex, the olfactory bulb, the rostral migratory pathway (RMP) and the hippocampus [4].
• We reveal that, in primary hippocampal neurons, STEF/Tiam1 are localized within growth cones and essential for formation of growth cone lamellipodia, eventually contributing to neurite growth [1].

Associations of Tiam2 with chemical compounds

• STEF (Sif- and Tiam1-like exchange factor), a guanine nucleotide exchange factor, was identified as a candidate molecule in regulation of neural development [4].

Regulatory relationships of Tiam2

• We also show that RhoA inhibits the STEF/Tiam1-Rac1 pathway [1].

Other interactions of Tiam2

• These data are used to propose a model that extracellular and intracellular information is integrated by STEF/Tiam1 to modulate the balance of Rho GTPase activities in the growth cone and, consequently, to control growth cone behavior [1].

References