Biomaterial Database

CD45 cross-linking regulates phospholipase C activation and tyrosine phosphorylation of specific substrates in CD3/Ti-stimulated T cells. 1991

J A Ledbetter, and G L Schieven, and F M Uckun, and J B Imboden

Bristol-Myers Squibb Corporation, Seattle, WA 98121.

In lymphocytes, CD45 regulates the increase in cytoplasmic calcium concentration that occurs after receptor cross-linking. Here we show that T cell receptor complex (CD3/Ti)-mediated inositol phosphate production was inhibited by CD45 ligation in Jurkat cells. CD3/Ti signaling in normal T cells was also inhibited by CD45 ligation, but coupling of CD4 with CD3/Ti gave augmented calcium signals that were entirely resistant to the inhibitory effect of CD45. In contrast, CD3-induced T cell proliferation was suppressed by immobilized CD45 mAb even in the presence of CD4 mAb. The effect of CD45 and CD4 ligation on tyrosine phosphorylation during T cell activation was directly examined by immunoblotting with anti-phosphotyrosine. Using immobilized mAb, CD45 ligation suppressed the tyrosine phosphorylation of specific substrates induced by CD3/Ti stimulation, including almost complete suppression of 150-, 36-, and 35-kDa proteins and partial suppression of 76- and 80-kDa proteins. Other tyrosine-phosphorylated proteins induced by CD3/Ti stimulation, including 135- and 21-kDa proteins, were not suppressed by simultaneous ligation of CD3/Ti and CD45. Simultaneous ligation of CD3 and CD4 enhanced tyrosine phosphorylation of all substrates, but did not overcome the CD45-mediated suppression of tyrosine phosphorylation of the 35- and 36-kDa proteins. The CD45-mediated suppression of phospholipase C activation is therefore modulated by association with CD4 without altering the specific inhibition of tyrosine phosphorylation and T cell proliferation after co-ligation of CD45 and CD3/Ti.

UI	MeSH Term	Description	Entries
D007295	Inositol Phosphates	Phosphoric acid esters of inositol. They include mono- and polyphosphoric acid esters, with the exception of inositol hexaphosphate which is PHYTIC ACID.	Inositol Phosphate,Phosphate, Inositol,Phosphates, Inositol
D008213	Lymphocyte Activation	Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.	Blast Transformation,Blastogenesis,Lymphoblast Transformation,Lymphocyte Stimulation,Lymphocyte Transformation,Transformation, Blast,Transformation, Lymphoblast,Transformation, Lymphocyte,Activation, Lymphocyte,Stimulation, Lymphocyte
D008970	Molecular Weight	The sum of the weight of all the atoms in a molecule.	Molecular Weights,Weight, Molecular,Weights, Molecular
D010727	Phosphoric Diester Hydrolases	A class of enzymes that catalyze the hydrolysis of one of the two ester bonds in a phosphodiester compound. EC 3.1.4.	Phosphodiesterase,Phosphodiesterases,Hydrolases, Phosphoric Diester
D010766	Phosphorylation	The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.	Phosphorylations
D011948	Receptors, Antigen, T-Cell	Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (CD3 COMPLEX). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.	Antigen Receptors, T-Cell,T-Cell Receptors,Receptors, T-Cell Antigen,T-Cell Antigen Receptor,T-Cell Receptor,Antigen Receptor, T-Cell,Antigen Receptors, T Cell,Receptor, T-Cell,Receptor, T-Cell Antigen,Receptors, T Cell Antigen,Receptors, T-Cell,T Cell Antigen Receptor,T Cell Receptor,T Cell Receptors,T-Cell Antigen Receptors
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002455	Cell Division	The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.	M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D003432	Cross-Linking Reagents	Reagents with two reactive groups, usually at opposite ends of the molecule, that are capable of reacting with and thereby forming bridges between side chains of amino acids in proteins; the locations of naturally reactive areas within proteins can thereby be identified; may also be used for other macromolecules, like glycoproteins, nucleic acids, or other.	Bifunctional Reagent,Bifunctional Reagents,Cross Linking Reagent,Crosslinking Reagent,Cross Linking Reagents,Crosslinking Reagents,Linking Reagent, Cross,Linking Reagents, Cross,Reagent, Bifunctional,Reagent, Cross Linking,Reagent, Crosslinking,Reagents, Bifunctional,Reagents, Cross Linking,Reagents, Cross-Linking,Reagents, Crosslinking