IL-2 signaling controls actin organization through Rho-like protein family, phosphatidylinositol 3-kinase, and protein kinase C-zeta.
IL-2 and IL-4 induce proliferation of TS1 alpha beta cells. Activation of the zeta isoform of protein kinase C is an important step in IL-2-, but not IL-4-mediated proliferation. In addition, protein kinase C-zeta is implicated in IL-2-mediated actin organization. Given the established involvement of the Rho family of small guanine nucleotide-binding proteins in organization of actin structures, we analyze the possible relationships between Rho and protein kinase C-zeta. Using the Rho-like protein family-specific toxin B from Clostridium difficile, we report in this work that IL-2, but not IL-4, induces a Rho-dependent activation of protein kinase C-zeta. This signaling event is mediated by the activation of phosphatidylinositol 3-kinase. In contrast, IL-4 induces a Rho-independent, phosphatidylinositol 3-kinase-mediated activation of protein kinase C-zeta, but this pathway has no implications in cytoskeleton organization.
Gómez
J
J
National Center of Biotechnology-CSIC, Center of Molecular Biology, Madrid, Spain.
García
A
A
R-Borlado
L
L
Bonay
P
P
Martínez-A
C
C
Silva
A
A
Fresno
M
M
Carrera
A C
AC
Eicher-Streiber
C
C
Rebollo
A
A
D000199:Actins / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000494:pharmacology; D002460:Cell Line; D016360:Clostridioides difficile / Q000276:immunology; D004789:Enzyme Activation / Q000276:immunology; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000199:Actins; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D019204:GTP-Binding Proteins; D007376:Interleukin-2; D015847:Interleukin-4; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011493:Protein Kinase C; C031815:toxB protein, Clostridium difficile