Separation of integrin-dependent adhesion from morphological changes based on differential PLC specificities.
In normal lymphocytes an inside-out signal up-regulating integrin adhesion is followed by a ligand-mediated outside-in cell spreading signal. Protein kinase C (PKC) inhibition blocks lymphocyte adherence to and spreading on fibronectin. In contrast, putative PLC inhibitors yield distinct differences with respect to adhesion and morphology. The phosphatidylinositol-specific phospholipase C (PLC) inhibitor neomycin blocked spreading of CD3/CD28-activated T cells on fibronectin by disrupting adhesion. Furthermore, when an additional inside-out signal for fibronectin adhesion is unnecessary such as with HPB-ALL T leukemic or phorbol-myristate-acetate-treated normal T cells, neomycin treatment does not alter adhesion or morphology. However, the phosphatidylcholine-specific PLC inhibitor D609 abrogates cell spreading without affecting adhesion to fibronectin in these cells as well as the CD3/CD28-activated T cells. These results strongly suggest that inside-out signaling for the integrin alpha4beta1 in lymphocytes proceeds through phosphatidylinositol-specific PLC and PKC, whereas the outside-in signal utilizes phosphatidylcholine-specific PLC and PKC.
Wooten
D K
DK
Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Teague
T K
TK
McIntyre
B W
BW
D000470:Alkaloids; D053119:Benzophenanthridines; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000502:physiology*; D015458:Leukemia, T-Cell / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D009355:Neomycin / Q000494:pharmacology; D009636:Norbornanes; D010617:Phenanthridines / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013379:Substrate Specificity; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000470:Alkaloids; D053119:Benzophenanthridines; D001952:Bridged-Ring Compounds; D004791:Enzyme Inhibitors; D005353:Fibronectins; D016023:Integrins; D009636:Norbornanes; D010617:Phenanthridines; D010726:Phosphodiesterase Inhibitors; D011500:Protein Synthesis Inhibitors; D013859:Thiocarbamates; D013871:Thiones; C046498:tricyclodecane-9-yl-xanthogenate; C016299:chelerythrine; D011493:Protein Kinase C; D010738:Type C Phospholipases; D009355:Neomycin