Activation of Src-like protein-tyrosine kinase Lyn and its association with phosphatidylinositol 3-kinase upon B-cell antigen receptor-mediated signaling.

Abstract

Crosslinking of membrane-bound IMmuno- (5-7). Associations of the interleukin 2 receptor f3 chain and T-cell antigen receptor with the Src-like kinases Lck and Fyn, respectively, were also reported (8-10). However, the physiological substrates or targets of these Src-like kinases in receptor-mediated signaling have yet to be identified. In recent studies on the targets of the tyrosine kinases, much information has been obtained about the plateletderived growth factor receptor (PDGF-R). The binding of PDGF to PDGF-R (J3 type) activates the receptor's kinase activity and induces its association with tyrosine-phosphorylated proteins such as phosphatidylinositol 3-kinase (PI 3-kinase), Ras GTPase-activating protein, and phospholipase C-y upon ligand-mediated signaling (11). One possible target of the tyrosine kinase, PI 3-kinase, is also associated with ligand-stimulated receptors for colony-stimulating factor 1 and insulin (11)(12)(13) and with an activated form of Src, p60-src (14). The levels ofproducts of PI 3-kinase are elevated in cells carrying these activated tyrosine kinases. Therefore, PI 3-kinase is likely to be an important target oftyrosine kinases.The lyn gene is a member of the src family and encodes two forms of protein-tyrosine kinase (Lyn), p531Yfl and p56IYn. 1118The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Association of a four–amino acid residue insertion polymorphism of the HS1 gene with systemic lupus erythematosus: Molecular and functional analysis

“…Upon BCR activation, HS1 is rapidly phosphorylated by Lyn and Syk (26), translocates to the nucleus, and induces a B cell response. HS1 contains several structurally distinct motifs, including 3 1 ⁄2 repeats of a unique .68 Ϯ 2.51%, 2.92 Ϯ 1.89%, and 2.71 Ϯ 1.07%, respectively.…”

“…HS1 is an important signaling molecule in BCR-mediated signal transduction (25)(26)(27)(28)(29). The aberrant HS1 in this patient lacked 37 amino acid residues in its N-terminal region and was carried heterozygously.…”

A Filarial Nematode-Secreted Phosphorylcholine-Containing Glycoprotein Uncouples the B Cell Antigen Receptor from Extracellular Signal-Regulated Kinase-Mitogen-Activated Protein Kinase by Promoting the Surface Ig-Mediated Recruitment of Src Homology 2 Domain-Containing Tyrosine Phosphatase-1 and Pac-1 Mitogen-Activated Kinase-Phosphatase

“…SHP-1-specific phosphopeptide (RRLIEDAEpYAARG; 350 M) and 100 l of malachite green solution were added to each well, and the reaction was allowed to proceed at room temperature for 15 min. The A630 was measured for each sample, and the phosphate concentration was assessed with reference to a standard curve (16). Pac-1 activity was also assessed in anti-Lyn and anti-Erk2 immune complexes using a UBI kit by following the hydrolysis of p-nitrophenyl phosphate as described by the manufacturers.…”

Aberrant HS1 molecule in a patient with systemic lupus erythematosus

“…27 The amino acid sequence of HS1 contains a variety of structurally significant motifs, 27 including three and one-half times repeats of a unique 37 amino acid residue-motif in the N-terminal region that can form a helix-turn-helix structure frequently found in the DNA binding domain of various transcriptional factors, 39 followed by an acidic a-helix region localized in the central moiety, and an SH3 domain at its C-terminus (Figure 3b). After BCR cross-linking, HS1 is rapidly phosphorylated synergistically by Lyn and Syk, 40 translocates to the nucleus, and induces B-cell response. 32 For instance, HS1 has been shown to play a role in BCRmediated cell death of WEHI-231 B lymphoma cell line, [30][31][32] which has been used as a model for immature B cells.…”