Protein kinase D1 and the beta 1 integrin cytoplasmic domain control beta 1 integrin function via regulation of Rap1 activation.
The functional activity of integrins is dynamically regulated by T cell receptor stimulation and by protein kinase C (PKC). We report a novel function for the PKC effector protein kinase D1 (PKD1) in integrin activation. Constitutively active and kinase-inactive PKD1 mutants lacking the PKD1 pleckstrin homology (PH) domain block phorbol ester- and TCR-mediated activation and clustering of beta1 integrins. The PH domain of PKD1 mediates the association of PKD1 with the GTPase Rap1 and is central to Rap1 activation and membrane translocation in T cells. Furthermore, PKD1 and Rap1 associate with beta1 integrins in a manner that is dependent on the carboxy-terminal end of the beta1 integrin subunit cytoplasmic domain. beta1 integrin expression is required for Rap1 activation and membrane localization of the PKD1-Rap1 complex. Therefore, PKD1 promotes integrin activation in T cells by regulating Rap1 activation and membrane translocation via interactions with the beta1 integrin subunit cytoplasmic domain.
Medeiros
Ricardo B
RB
Department of Laboratory Medicine and Pathology, Center for Immunology, Cancer Center, University of Minnesota Medical School, Minneapolis,55455, USA.
Dickey
Deborah M
DM
Chung
Heekyoung
H
Quale
Angie C
AC
Nagarajan
Lakshmi R
LR
Billadeau
Daniel D
DD
Shimizu
Yoji
Y
D002448:Cell Adhesion / Q000502:physiology; D003593:Cytoplasm / Q000201:enzymology / Q000276:immunology; D005353:Fibronectins / Q000502:physiology; D017930:Genes, Reporter; D006801:Humans; D019012:Integrin beta1 / Q000502:physiology*; D019169:Jurkat Cells; D009154:Mutation; D011493:Protein Kinase C / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics; D013601:T-Lymphocytes / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism*
D005353:Fibronectins; D019012:Integrin beta1; D011993:Recombinant Fusion Proteins; C089212:protein kinase D; D011493:Protein Kinase C; D020827:rap1 GTP-Binding Proteins