Protein kinase D isoforms are dispensable for integrin-mediated lymphocyte adhesion and homing to lymphoid tissues.
Leukocyte function-associated antigen-1 (LFA-1) and very late antigen-4 (VLA-4) integrins are essential for lymphocyte adhesion, trafficking and effector functions. Protein kinase D (PKD) has previously been implicated in lymphocyte integrin regulation through regulation of Rap1 activity. However, the true role of PKD in integrin regulation in primary lymphocytes has not previously been investigated. The major PKD isoform in lymphocytes is PKD2. Here we employed PKD2-deficient mice, a specific PKD kinase inhibitor, as well as PKD-null DT40 B cells to investigate the role of PKD in integrin regulation in lymphocytes. We report that PKD2-deficient lymphocytes bound normally to integrin ligands in static and shear flow adhesion assays. They also homed normally to lymphoid organs after adoptive transfer into wild-type mice. DT40 B cells devoid of any PKD isoforms and primary lymphocytes pretreated with a specific PKD inhibitor bound normally to integrin ligands, indicating that multiple PKD isoforms do not redundantly regulate lymphocyte integrins. In addition, PKD2-deficient lymphocytes, as well as DT40 cells devoid of any PKD isoforms, could activate Rap1 in response to B-cell receptor ligation or phorbol ester treatment. Together, these results show that the PKD family does not play a critical role in lymphocyte integrin-mediated cell adhesion or lymphocyte trafficking in vivo.
Medical Research Institute, Ninewells Hospital and Medical School University of Dundee, Dundee, UK. s.matthews@dundee.ac.uk
Sharon A
SA
Matthews
Hwee
H
San Lek
Vicky L
VL
Morrison
Matthew G
MG
Mackenzie
Marouan
M
Zarrouk
Doreen
D
Cantrell
Susanna C
SC
Fagerholm
D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology; D002448:Cell Adhesion; D002478:Cells, Cultured; D020690:GTPase-Activating Proteins / Q000378:metabolism; D016023:Integrins / Q000737:chemistry / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008214:Lymphocytes / Q000201:enzymology / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology*; D051379:Mice; D010703:Phorbol Esters / Q000378:metabolism; D000091283:Protein Kinase D2; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism
D020690:GTPase-Activating Proteins; D016023:Integrins; D007527:Isoenzymes; D010703:Phorbol Esters; D000091283:Protein Kinase D2; C539504:Rap1GAP protein, mouse; D011947:Receptors, Antigen, B-Cell; D011494:Protein Kinases