Here we present a 2.0-A crystal structure of Galpha i in complex with the GEM motif of GIV/Girdin. Nucleotide exchange assays molecular dynamics simulations and hydrogen-deuterium exchange experiments demonstrate that GEM binding to the conformational switch II causes structural changes that allosterically propagate to the hydrophobic core of the Galpha i GTPase domain
Results showed a role of Girdin in the collective invasion of skin cancer cells where it interacts with beta-catenin. Also Girdin is indispensable for stable cell-cell interaction supracellular cytoskeletal organization and the collective migration of cancer.
Together this study shows a novel cytoprotective role for GIV in ER-stressed cells and furthers our understanding of the mechanisms that contribute to cell survival during ER stress.
Study revealed that the downregulation of the expression of Girdin can inhibit the proliferation invasion and migration of colorectal cancer cells through decrease in proinflammatory cytokine production and inhibition of JAK/STAT signaling.
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