Tyrosine kinase activity associated with the CD7 antigen: correlation with regulation of T cell integrin function.
Rapid up-regulation of the functional activity of integrin adhesion receptors is a hallmark of T cell activation. Monoclonal antibody engagement of the CD7 antigen on human T cells results in an increase in beta 1 and beta 2 integrin-mediated adhesion within minutes. This suggests that CD7 is capable of transducing intracellular signals, and is consistent with other indirect studies implicating CD7 as a signaling receptor on T cells. In this report, we have explored the intracellular mechanism by which CD7 modulates integrin functional activity. First, CD7-mediated up-regulation of T cell adhesion was found to be unique when compared to phorbol ester stimulation and CD3/T cell receptor cross-linking, based on differences in the kinetics of activation-dependent integrin-mediated adhesion and lack of increase in CD2 functional activity. Second, up-regulation of integrin activity mediated by CD7 cross-linking was completely inhibited by the tyrosine kinase inhibitor herbimycin A. Third, antiphosphotyrosine immunoblotting demonstrated that antibody engagement of CD7 results in a rapid but transient increase in tyrosine phosphorylation in human T cells. Finally, CD7 immunoprecipitates contain in vitro kinase activity, as demonstrated by phosphorylation of a predominant band of 80 kDa and multiple other bands. Phosphoamino acid analysis of the 80-kDa substrate revealed phosphorylation on tyrosine as well as serine and threonine residues. Together, our results suggest that CD7 is associated with tyrosine kinase activity and that this tyrosine kinase activity correlates with the ability of CD7 to regulate T cell integrin functional activity.
Chan
A S
AS
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor.
Reynolds
P J
PJ
Shimizu
Y
Y
D015703:Antigens, CD / Q000502:physiology*; D019011:Antigens, CD7; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D016227:Benzoquinones; D002448:Cell Adhesion; D005353:Fibronectins / Q000502:physiology; D006801:Humans; D016023:Integrins / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D047029:Lactams, Macrocyclic; D010766:Phosphorylation; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D013601:T-Lymphocytes / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism; D015854:Up-Regulation
D015703:Antigens, CD; D019011:Antigens, CD7; D000945:Antigens, Differentiation, T-Lymphocyte; D016227:Benzoquinones; D005353:Fibronectins; D016023:Integrins; D047029:Lactams, Macrocyclic; D011809:Quinones; D018799:Intercellular Adhesion Molecule-1; D017828:Rifabutin; D014443:Tyrosine; C020754:herbimycin; D011505:Protein-Tyrosine Kinases