Apoptosis signal-regulating kinase (ASK)-1 mediates apoptosis through activation of JNK1 following engagement of membrane immunoglobulin

Treatment of B lymphocytes with antibodies to membrane immunoglobulin (Ig) stimulates protein tyrosine phosphorylation. We have examined the phosphorylation in vitro of proteins associated with membrane Ig. The Src family protein tyrosine kinases p53/56lyn, p59fyn, and p56lck are associated with membrane Ig in spleen B cells and B-cell lines and undergo phosphorylation in vitro. The pattern of expression of Src family protein tyrosine kinases in B cells varied. Our studies suggest that multiple kinases can potentially interact with membrane Ig and that within any one B-cell type, all of the Src family kinases expressed can be found in association with membrane Ig. We also observed that the Ig-associated Ig alpha protein, multiple forms of Ig beta, and proteins of 100 and 25 kDa were tyrosine phosphorylated in vitro. The 100- and 25-kDa proteins remain unidentified.

Download Full-text

Activation of channel catfish B cells by membrane immunoglobulin cross-linking

Developmental & Comparative Immunology ◽

10.1016/0145-305x(94)90238-0 ◽

1994 ◽

Vol 18 (2) ◽

pp. 97-107 ◽

Cited By ~ 28

Author(s):

Frederik W. van Ginkel ◽

Norman W. Miller ◽

Marvin A. Cuchens ◽

L.William Clem

Keyword(s):

B Cells ◽

Channel Catfish ◽

Cross Linking ◽

Membrane Immunoglobulin

Download Full-text

Selective activation of p42 mitogen-activated protein (MAP) kinase in murine B lymphoma cell lines by membrane immunoglobulin cross-linking. Evidence for protein kinase C-independent and -dependent mechanisms of activation

Biochemical Journal ◽

10.1042/bj2870269 ◽

1992 ◽

Vol 287 (1) ◽

pp. 269-276 ◽

Cited By ~ 40

Author(s):

M R Gold ◽

J S Sanghera ◽

J Stewart ◽

S L Pelech

Keyword(s):

Map Kinase ◽

Tyrosine Phosphorylation ◽

Cell Lines ◽

Map Kinases ◽

Phorbol Esters ◽

Cross Linking ◽

Kinase Activation ◽

Membrane Immunoglobulin ◽

Protein Map ◽

Mitogen Activated Protein

Cross-linking of membrane immunoglobulin (mIg), the B lymphocyte antigen receptor, with anti-receptor antibodies stimulates tyrosine phosphorylation of a number of proteins, including one of 42 kDa. Proteins with a similar molecular mass are tyrosine-phosphorylated in response to receptor stimulation in other cell types and have been identified as serine/threonine kinases, termed mitogen-activated protein (MAP) kinases or extracellular signal-regulated kinases (ERKs). The MAP kinases constitute a family of related kinases, at least three of which have molecular masses of 40-45 kDa. In this paper we show that mIg cross-linking stimulated the myelin basic protein phosphotransferase activity characteristic of MAP kinase in both mature and immature murine B cell lines. This enzyme activity co-purified on three different columns with a 42 kDa protein that was tyrosine-phosphorylated (pp42) in response to mIg cross-linking and which reacted with a panel of anti-(MAP kinase) antibodies. Although immunoblotting with the anti-(MAP kinase) antibodies showed that these B cell lines expressed both 42 kDa and 44 kDa forms of MAP kinase, only the 42 kDa form was activated and tyrosine-phosphorylated to a significant extent. Activation of protein kinase C (PKC) with phorbol esters also resulted in selective tyrosine phosphorylation and activation of the 42 kDa MAP kinase. This suggested that mIg-induced MAP kinase activation could be due to stimulation of PKC by mIg. However, mIg-stimulated MAP kinase activation and pp42 tyrosine phosphorylation was only partially blocked by a PKC inhibitor, the staurosporine analogue Compound 3. In contrast, Compound 3 completely blocked the ability of phorbol esters to stimulate MAP kinase activity and induce tyrosine phosphorylation of pp42. Thus mIg may activate MAP kinase by both PKC-dependent and -independent mechanisms.

Download Full-text

Functional dissection of the CD21/CD19/TAPA-1/Leu-13 complex of B lymphocytes.

Journal of Experimental Medicine ◽

10.1084/jem.178.4.1407 ◽

1993 ◽

Vol 178 (4) ◽

pp. 1407-1417 ◽

Cited By ~ 167

Author(s):

A K Matsumoto ◽

D R Martin ◽

R H Carter ◽

L B Klickstein ◽

J M Ahearn ◽

...

Keyword(s):

B Lymphocytes ◽

Protein Complexes ◽

Pi3 Kinase ◽

Free Calcium ◽

Wild Type ◽

Extracellular Domains ◽

Membrane Immunoglobulin ◽

Low Concentrations ◽

Cellular Aggregation ◽

Membrane Protein Complexes

The CD21/CD19/TAPA-1 complex of B lymphocytes amplifies signal transduction through membrane immunoglobulin (mIg), recruits phosphatidylinositol 3-kinase (PI3-kinase), and induces homotypic cellular aggregation. The complex is unique among known membrane protein complexes of the immune system because its components represent different protein families, and can be expressed individually. By constructing chimeric molecules replacing the extracellular, transmembrane, and cytoplasmic regions of CD19 and CD21 with those of HLA-A2 and CD4, we have determined that CD19 and TAPA-1 interact through their extracellular domains, CD19 and CD21 through their extracellular and transmembrane domains, and, in a separate complex, CD21 and CD35 through their extracellular domains. A chimeric form of CD19 that does not interact with CD21 or TAPA-1 was expressed in Daudi B lymphoblastoid cells and was shown to replicate two functions of wild-type CD19 contained within the complex: synergistic interaction with mIgM to increase intracellular free calcium and tyrosine phosphorylation and association with the p85 subunit of PI3-kinase after ligation of mIgM. The chimeric CD19 lacked the capacity of the wild-type CD19 to induce homotypic cellular aggregation, a function of the complex that can be ascribed to the TAPA-1 component. The CD21/CD19/TAPA-1 complex brings together independently functioning subunits to enable the B cell to respond to low concentrations of antigen.

Download Full-text