Clustering the adhesion molecules VLA‐4 (CD49d/CD29) in Jurkat T cells or VCAM‐1 (CD106) in endothelial (ECV 304) cells activates the phosphoinositide pathway and triggers Ca²⁺ mobilization

Abstract

Ligation of very late antigen (VLA)-4 (alpha 4 beta 1 integrin) with a cross-linked anti-alpha 4 subunit monoclonal antibody (mAb) triggered a biphasic Ca2+ response in Jurkat cell populations and in peripheral human lymphocytes. Cross-linking vascular cell adhesion molecule (VCAM)-1 (the counter-receptor of VLA-4) in ECV 304 endothelial cells generated a biphasic Ca2+ response. Tumor necrosis factor-alpha-primed human umbilical cord vascular endothelial cells also responded to the cross-linked mAb with a biphasic Ca2+ profile. Ligated VLA-4 (Jurkat cells) or VCAM-1 (ECV 304) stimulated the production of myo-inositol 1,4,5-trisphosphate. ECV 304 cells induced a biphasic Ca2+ response in Fura2-loaded Jurkat cells, whereas a transient response was observed when Jurkat cells were added to Fura2-loaded ECV 304 cells. The Ca2+ responses in these experiments involved VLA-4/VCAM-1 interactions since they were significantly reduced (approximately 80%) by prior treatment of the target cells with the relevant noncross-linked mAb. Close contact between the cells triggered mutual Ca2+ signaling as shown by spectrofluorimetric and confocal microscopy time-dependent recordings. Fibronectin and its CS-1 fragment (V25) triggered a sustained Ca2+ response in Jurkat cells (confocal microscopy). Our results suggest that the VLA-4 and VCAM-1 adhesion molecules can transduce a signal that involves activation of the phosphoinositide pathway and the mobilization of Ca2+.

α4 Integrin Signaling Activates Phosphatidylinositol 3-Kinase and Stimulates T Cell Adhesion to Intercellular Adhesion Molecule-1 to a Similar Extent As CD3, but Induces a Distinct Rearrangement of the Actin Cytoskeleton

“…In monocytes, a urokinase receptordependent pathway regulated the ␣ 4 integrin-mediated activation of ␤ 2 integrins (15). Other pathways involved in ␤ 2 integrin adhesion are also activated by ␣ 4 (or ␤ 1 ) integrins and may play additional roles in this signaling cascade (24,30). In this paper, we investigated the role of PI 3-kinase and ERK1/2.…”

Role of ?1 integrins in adhesion and invasion of hepatocellular carcinoma cells

“…50,51 HCC cells that have an expression of ␤1 integrins with naturally acquired high constitutive activities are supposed to be capable of keeping the necessary balance of adhesion and release by means of coordinative activation and inactivation of integrins. Recent studies have revealed that integrin-ligand interactions elicit a variety of intracellular signaling including the stimulation of protein kinase C activity, 53 Na ϩ /H ϩ antiporter activity, 54 and phosphoinositide hydrolysis, 55 in addition to the elevation of intracellular free Ca 2ϩ levels 56 and GTP-bound p21 Ha-Ras levels. 57 Furthermore, integrin-initiated signals stimulate the tyrosine phosphorylation of a number of cellular proteins.…”

VCAM-1 Activates Phosphatidylinositol 3-Kinase and Induces p120CblPhosphorylation in Human Airway Smooth Muscle Cells

“…In contrast to the many studies of ICAM-1 and ICAM-3 signaling, little is known about the role of VCAM-1 in cellular activation, although two recent studies suggest that VCAM-1 engagement leads to cytoskeletal rearrangement, myoinositol production, and calcium mobilization (14,15).…”