scholarly journals The T-cell antigen CD5 acts as a receptor and substrate for the protein-tyrosine kinase p56lck.

1994 ◽  
Vol 14 (5) ◽  
pp. 2862-2870 ◽  
Author(s):  
M Raab ◽  
M Yamamoto ◽  
C E Rudd
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Expression System ◽  
Baculovirus Expression System ◽  
Protein Tyrosine ◽  
Cell Antigen ◽  
Tyrosine Residues ◽  
Baculovirus Expression

CD5 is a T-cell-specific antigen which binds to the B-cell antigen CD72 and acts as a coreceptor in the stimulation of T-cell growth. CD5 associates with the T-cell receptor zeta chain (TcR zeta)/CD3 complex and is rapidly phosphosphorylated on tyrosine residues as a result of TcR zeta/CD3 ligation. However, despite this, the mechanism by which CD5 generates intracellular signals is unclear. In this study, we demonstrate that CD5 is coupled to the protein-tyrosine kinase p56lck and can act as a substrate for p56lck. Coexpression of CD5 with p56lck in the baculovirus expression system resulted in the phosphorylation of CD5 on tyrosine residues. Further, anti-CD5 and anti-p56lck coprecipitated each other in a variety of detergents, including Nonidet P-40 and Triton X-100. Anti-CD5 also precipitated the kinase from various T cells irrespective of the expression of TcR zeta/CD3 or CD4. No binding between p59fyn(T) and CD5 was detected in T cells. The binding of p56lck to CD5 induced a 10- to 15-fold increase in p56lck catalytic activity, as measured by in vitro kinase analysis. In vivo labelling with 32P(i) also showed a four- to fivefold increase in Y-394 occupancy in p56lck when associated with CD5. The use of glutathione S-transferase-Lck fusion proteins in precipitation analysis showed that the SH2 domain of p56lck could recognize CD5 as expressed in the baculovirus expression system. CD5 interaction with p56lck represents a novel variant of a receptor-kinase complex in which receptor can also serve as substrate. The CD5-p56lck interaction is likely to play roles in T-cell signalling and T-B collaboration.

The T-cell antigen CD5 acts as a receptor and substrate for the protein-tyrosine kinase p56lck

1994 ◽  
Vol 14 (5) ◽  
pp. 2862-2870
Author(s):  
M Raab ◽  
M Yamamoto ◽  
C E Rudd
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Expression System ◽  
Baculovirus Expression System ◽  
Protein Tyrosine ◽  
Cell Antigen ◽  
Tyrosine Residues ◽  
Baculovirus Expression

CD5 is a T-cell-specific antigen which binds to the B-cell antigen CD72 and acts as a coreceptor in the stimulation of T-cell growth. CD5 associates with the T-cell receptor zeta chain (TcR zeta)/CD3 complex and is rapidly phosphosphorylated on tyrosine residues as a result of TcR zeta/CD3 ligation. However, despite this, the mechanism by which CD5 generates intracellular signals is unclear. In this study, we demonstrate that CD5 is coupled to the protein-tyrosine kinase p56lck and can act as a substrate for p56lck. Coexpression of CD5 with p56lck in the baculovirus expression system resulted in the phosphorylation of CD5 on tyrosine residues. Further, anti-CD5 and anti-p56lck coprecipitated each other in a variety of detergents, including Nonidet P-40 and Triton X-100. Anti-CD5 also precipitated the kinase from various T cells irrespective of the expression of TcR zeta/CD3 or CD4. No binding between p59fyn(T) and CD5 was detected in T cells. The binding of p56lck to CD5 induced a 10- to 15-fold increase in p56lck catalytic activity, as measured by in vitro kinase analysis. In vivo labelling with 32P(i) also showed a four- to fivefold increase in Y-394 occupancy in p56lck when associated with CD5. The use of glutathione S-transferase-Lck fusion proteins in precipitation analysis showed that the SH2 domain of p56lck could recognize CD5 as expressed in the baculovirus expression system. CD5 interaction with p56lck represents a novel variant of a receptor-kinase complex in which receptor can also serve as substrate. The CD5-p56lck interaction is likely to play roles in T-cell signalling and T-B collaboration.

The CD4/CD8:p56lck complex in T lymphocytes: a potential mechanism to regulate T-cell growth

1989 ◽  
Vol 67 (9) ◽  
pp. 581-589 ◽  
Author(s):  
Christopher Rudd ◽  
Stuart Helms ◽  
Elizabeth K. Barber ◽  
Stuart F. Schlossman
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Growth ◽  
T Lymphocytes ◽  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Active Form ◽  
Protein Tyrosine ◽  
Catalytically Active ◽  
T Cell Growth

The CD4 and CD8 antigens on the surface of T cells appear to bind to major histocompatibility complex (MHC) class II and I antigens, respectively. These receptors have also been found to regulate T cell growth in a manner independent of MHC recognition. In this report, we describe recent work showing that the CD4 and CD8 receptors are coupled to a protein-tyrosine kinase, p56lck, from T lymphocytes. The p56lck protein is a member of the src family, which plays a crucial role in the activation and transformation of various mammalian cells. The CD4/CD8:p56ck complex is catalytically active as shown by its ability to phosphorylate at 55–60 kDa. Two-dimensional, nonequilibrium gel electrophoresis demonstrated the similarity of p56lck associated with the CD4 and CD8 antigens. Detergents were found to vary in their ability to solubilize the CD4:p56lck complex in a catalytically active form. We further demonstrated by in vitro phosphorylation that members of the CD3 complex including the γ, δ, and ε chains, as well as a putative ζ subunit can be phosphorylated at tyrosyl residues by the CD4/CD8:p56lck complex. Thus, this interaction may play an important role in the activation of T cells, and may mediate the cooperative interaction between the CD4/CD8 antigens and the Ti(TcR)/CD3 complex. This interaction also represents a possible precedent by which other members of the src family (c-src, c-yes, c-fgr, etc.) may be found to interact with mammalian growth receptors.Key words: CD4, CD8, protein-tyrosine kinase p56lck.

scholarly journals Association of the tyrosine kinase LCK with phospholipase C-gamma 1 after stimulation of the T cell antigen receptor.

1992 ◽  
Vol 176 (2) ◽  
pp. 373-379 ◽  
Author(s):  
J R Weber ◽  
G M Bell ◽  
M Y Han ◽  
T Pawson ◽  
J B Imboden
Keyword(s):  
T Cell ◽  
Tyrosine Kinase ◽  
Phospholipase C ◽  
Protein Tyrosine Kinase ◽  
Antigen Receptor ◽  
T Cell Antigen Receptor ◽  
Cell Antigen Receptor ◽  
Protein Tyrosine ◽  
Cell Antigen ◽  
Stimulation Of

Stimulation of the T cell antigen receptor (TCR) activates a protein tyrosine kinase and leads to the tyrosine phosphorylation of phosphoinositide-specific phospholipase C-gamma 1 (PLC gamma 1). The molecular interactions involved in this phosphorylation are not known. After stimulation of the TCR on Jurkat T cells, tyrosine-phosphorylated proteins of 36, 38, 58, and 63 kD coprecipitate with PLC gamma 1. An identical pattern of proteins precipitate with TrpE fusion proteins that contain the Src homology (SH) 2 domains of PLC gamma 1, indicating that these regions of PLC gamma 1 are responsible for binding. TCR stimulation leads to an association between the SH2 domains of PLC gamma 1 and a protein tyrosine kinase, which, by peptide mapping, is identical to p56lck. These studies establish that p56lck associates with PLC gamma 1 as a result of TCR stimulation of Jurkat cells, suggesting that p56lck plays a central role in coupling the TCR to the activation of PLC gamma 1.

Sign in / Sign up

Export Citation Format

Share Document