TI - AILIM/ICOS -mediated elongation of activated T cells is regulated by both the PI3-kinase/Akt and Rho family cascade . AB - T - cell migration and movement is a critical component of a fully functional immune system . Activation-inducible lymphocyte immunomediatory molecule/inducible co-stimulator ( AILIM/ICOS ) , which is a member of CD28 co-stimulatory receptor family , induces both activated T-cell migration underneath tumor necrosis factor alpha-treated human umbilical vein endothelial cell layers and also the morphological polarization of activated T cells . In our current study , we have investigated the signaling mechanisms underlying the morphological polarization of activated T cells , initiated by AILIM/ICOS signaling . AILIM/ICOS signaling induces the activation of phosphoinositide-3 ( PI3 ) -kinase , the product of which , phosphatidylinositol 3,4,5-trisphosphate ( PIP3 ) , was found to be localized in the lamellipodia at the front part of the cells . Phosphorylated Akt is also co-localized with PIP3 and filamentous actin in lamellipodia and the PI3-kinase/Akt signaling cascade has critical roles in T-cell polarization and lamellipodia formation via the re-organization of the actin cytoskeleton . Rho family members and their downstream effectors , Rho-associated kinase and p21-activated kinase ( PAK ) , are also involved in AILIM/ICOS -mediated elongation . The PAK family members are serine/threonine kinase downstream effectors of both Rac and Cdc42 . PAK3 is induced by the activation of T cells , whereas PAK1 is constitutively expressed in both naive and activated T cells . During the elongation , not only PAK1 but also PAK3 play an essential role through the phosphorylation of their conservative autophosphorylation sites and catalytic domain . Ser-244 phosphorylation , which is a putative Akt phosphorylation site , on PAK3 but not on PAK1 also regulates the morphological polarization of activated T cells by AILIM/ICOS signaling . Both the PI3-kinase/Akt and Rho family cascades operate coordinately to induce the forward migration of activated T cells by AILIM/ICOS signaling .