Total synthesis of natural 20(S)-camptothecin

Ej, Corey; Dn, Crouse; Je, Anderson

doi:10.1021/jo00902a034

Cited by 107 publications

(33 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Surprisingly, the studies using a panel of different tyrosine kinases (Fig. 8) have identified Lck, an Src family kinase where a link to B-cell signaling was not confirmed in all studies (10,32,33,34), as a tyrosine kinase that can efficiently phosphorylate a peptide incorporating Tyr 753 and Tyr 759 residues of PLC␥2. Protein-tyrosine kinase Syk has also been implicated in Bcell signaling and shown to be required for both PLC␥2 phosphorylation and calcium responses (10).…”

Section: Discussionmentioning

confidence: 96%

Tyrosine Residues in Phospholipase Cγ2 Essential for the Enzyme Function in B-cell Signaling

Rodriguez¹,

Matsuda²,

Perišić

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

Phospholipase C␥ (PLC␥) isoforms are regulated through activation of tyrosine kinase-linked receptors. The importance of growth factor-stimulated phosphorylation of specific tyrosine residues has been documented for PLC␥1; however, despite the critical importance of PLC␥2 in B-cell signal transduction, neither the tyrosine kinase(s) that directly phosphorylate PLC␥2 nor the sites in PLC␥2 that become phosphorylated after stimulation are known. By measuring the ability of human PLC␥2 to restore calcium responses to the B-cell receptor stimulation or oxidative stress in a B-cell line (DT40) deficient in PLC␥2, we have demonstrated that two tyrosine residues, Tyr 753 and Tyr 759 , were important for the PLC␥2 signaling function. Furthermore, the double mutation Y753F/Y759F in PLC␥2 resulted in a loss of tyrosine phosphorylation in stimulated DT40 cells. Of the two kinases that previously have been proposed to phosphorylate PLC␥2, Btk, and Syk, purified Btk had much greater ability to phosphorylate recombinant PLC␥2 in vitro, whereas Syk efficiently phosphorylated adapter protein BLNK. Using purified proteins to analyze the formation of complexes, we suggest that function of Syk is to phosphorylate BLNK, providing binding sites for PLC␥2. Further analysis of PLC␥2 tyrosine residues phosphorylated by Btk and several kinases from the Src family has suggested multiple sites of phosphorylation and, in the context of a peptide incorporating residues Tyr 753 and Tyr 759 , shown preferential phosphorylation of Tyr 753 .

show abstract

Section: Discussionmentioning

confidence: 96%

Tyrosine Residues in Phospholipase Cγ2 Essential for the Enzyme Function in B-cell Signaling

Rodriguez¹,

Matsuda²,

Perišić

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…It is possible that the Src kinase pathway alone is unable to activate all of the necessary signaling proteins essential for efficient Kit-induced proliferation, although Src kinases have been shown to regulate multiple signaling pathways, including the activation of the Ras pathway via Shc, the PI 3-kinase/Akt pathway via Cbl, and the Rac/c-Jun N-terminal kinase pathway via guanine exchange factors, such as Vav (29,47,48). Whether all of these signaling molecules are activated by Src kinases in response to Kit activation is currently being investigated.…”

Section: Discussionmentioning

confidence: 99%

Functional and Biochemical Consequences of Abrogating the Activation of Multiple Diverse Early Signaling Pathways in Kit

Tan

Munugalavadla

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

Kit receptor tyrosine kinase and erythropoietin receptor (Epo-R) cooperate in regulating blood cell development. Mice that lack the expression of Kit or Epo-R die in utero of severe anemia. Stimulation of Kit by its ligand, stem cell factor activates several distinct early signaling pathways, including phospholipase C␥, phosphatidylinositol 3-kinase, Src kinase, Grb2, and Grb7. The role of these pathways in Kit-induced growth, proliferation, or cooperation with Epo-R is not known. We demonstrate that inactivation of any one of these early signaling pathways in Kit significantly impairs growth and proliferation. However, inactivation of the Src pathway demonstrated the most profound defect. Combined stimulation with Epo also resulted in impaired cooperation between Src-defective Kit mutant and Epo-R and, to a lesser extent, with Kit mutants defective in the activation of phosphatidylinositol 3-kinase or Grb2. The impaired cooperation between the Src-defective Kit mutant and Epo-R was associated with reduced transphosphorylation of Epo-R and expression of c-Myc. Remarkably, restoration of only the Src pathway in a Kit receptor defective in the activation of all early signaling pathways demonstrated a 50% correction in proliferation in response to Kit stimulation and completely restored the cooperation with Epo-R. These data demonstrate an essential role for Src pathway in regulating growth, proliferation, and cooperation with Epo-R downstream from Kit. Receptor tyrosine kinases (RTKs)1 trigger multitude of cellular events, including proliferation, survival, differentiation, and migration. In response to ligand-induced stimulation, RTKs undergo dimerization and autophosphorylation on several distinct cytoplasmic tyrosine residues (1-4). These phosphorylated tyrosine residues become binding sites for a variety of Src homology 2 domain-containing enzymes and adaptor proteins such as phospholipase C␥ (PLC-␥), phosphatidylinositol 3-kinase p85 subunit (PI 3-kinase), Ras GTPase-activating protein, SHP2 phosphatase, Src kinases, Grb2, Grb7, and Shc (5). In this manner, the phosphorylated tyrosine residues initiate signal transduction via several distinct early signaling pathways. A major unresolved question in the field of RTK signaling is whether these diverse signaling pathways result in redundant or nonredundant biological functions. Recent studies utilizing the platelet-derived growth factor (PDGF) RTK have begun to address some of these issues in nonhematopoietic cells (6 -8). However, relatively little is known about the biological consequence(s) of activation of diverse signaling pathways by RTKs in hematopoietic cells.In hematopoietic cells, the RTK Kit plays an essential role in regulating proliferation, survival, differentiation, and migration of stem and progenitor cells (9 -11). The proto-oncogene Kit encodes the receptor for stem cell factor (SCF) and belongs to the type III receptor tyrosine kinase subfamily (9 -11). This family of cytokine receptor includes the macrophage colonystimulating factor (M-CSF) r...

show abstract

“…The regulation of Src family kinases is complex (28), and the activity of these kinases is influenced significantly by phosphorylation of specific tyrosine residues, e.g. Lyn is activated by phosphorylation of Tyr 397 , and inhibited by phosphorylation of Tyr 508 (29).…”

mentioning

confidence: 99%

Csk-binding Protein Mediates Sequential Enzymatic Down-regulation and Degradation of Lyn in Erythropoietin-stimulated Cells

et al. 2006

View full text Add to dashboard Cite

Total synthesis of natural 20(S)-camptothecin

Cited by 107 publications

References 3 publications

Tyrosine Residues in Phospholipase Cγ2 Essential for the Enzyme Function in B-cell Signaling

Tyrosine Residues in Phospholipase Cγ2 Essential for the Enzyme Function in B-cell Signaling

Functional and Biochemical Consequences of Abrogating the Activation of Multiple Diverse Early Signaling Pathways in Kit

Csk-binding Protein Mediates Sequential Enzymatic Down-regulation and Degradation of Lyn in Erythropoietin-stimulated Cells

Contact Info

Product

Resources

About