Constitutive membrane association potentiates activation of Bruton tyrosine kinase

Li, Tianjian; Rawlings, David J.; Park, Hyun Sun; Kato, Roberta M.; Witte, Owen N.; Satterthwaite, Anne B.

doi:10.1038/sj.onc.1201308

Cited by 64 publications

(53 citation statements)

References 52 publications

(107 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The interaction between the PH domains and phospholipids is thought to play a role in membrane recruitment of these kinases in response to extracellular stimuli. This is consistent with the reports that several Btk kinases are activated by PI3-kinase (August et al, 1997;Li et al, 1997a;Qiu et al, 1998b) and that Btk becomes membrane localized when PTEN a lipid phosphatase which counteracts PI3K is defective Shan et al, 2000).…”

Section: Interaction With Phosphoinositidessupporting

confidence: 81%

“…First, in a cell type that lacks PTEN, a lipid phosphatase which counteracts PI3K, Itk is constitutively localized on the plasma membrane and hypersensitive to T cell receptor activation (Shan et al, 2000). Second, the attachment of a myristylation site or the extracellular and transmembrane domain of cytokine receptor to Tec lead to constitutive activation and membrane localization, in the absence of PI3K activation (Li et al, 1997a;Yoshida et al, 2000). Third, the importance of unfolding the PH domain during activation is underscored by the ®nding that deletion of the PH domain leads to constitutive activation of Etk/Bmx in either prostate or lung epithelial cells (Qiu et al, 1998b;Wen et al, 1999).…”

Section: Upstream Activatorsmentioning

confidence: 99%

See 1 more Smart Citation

Signaling network of the Btk family kinases

Qiu¹,

2000

View full text Add to dashboard Cite

The Btk family kinases represent new members of nonreceptor tyrosine kinases, which include Btk/Atk, Itk/ Emt/Tsk, Bmx/Etk, and Tec. They are characterized by having four structural modules: PH (pleckstrin homology) domain, SH3 (Src homology 3) domain, SH2 (Src homology 2) domain and kinase (Src homology 1) domain. Increasing evidence suggests that, like Srcfamily kinases, Btk family kinases play central but diverse modulatory roles in various cellular processes. They participate in signal transduction in response to virtually all types of extracellular stimuli which are transmitted by growth factor receptors, cytokine receptors, G-protein coupled receptors, antigen-receptors and integrins. They are regulated by many non-receptor tyrosine kinases such as Src, Jak, Syk and FAK family kinases. In turn, they regulate many of major signaling pathways including those of PI3K, PLCg and PKC. Both genetic and biochemical approaches have been used to dissect the signaling pathways and elucidate their roles in growth, di erentiation and apoptosis. An emerging new role of this family of kinases is cytoskeletal reorganization and cell motility. The physiological importance of these kinases was amply demonstrated by their link to the development of immunode®ciency diseases, due to germ-line mutations. The present article attempts to review the structure and functions of Btk family kinases by summarizing our current knowledge on the interacting partners associated with the di erent modules of the kinases and the diverse signaling pathways in which they are involved. Oncogene (2000) 19, 5651 ± 5661.

show abstract

Section: Interaction With Phosphoinositidessupporting

confidence: 81%

Section: Upstream Activatorsmentioning

confidence: 99%

Signaling network of the Btk family kinases

Qiu¹,

2000

View full text Add to dashboard Cite

show abstract

“…This amino acid substitution was first described for Btk, where it increases Btk activity and Btk recruitment to the plasma membrane (52). Furthermore, in vitro binding experiments indicate that the Btk PH domain mutant, E41K, has increased binding to phosphoinositides.…”

Section: The Importance Of the Ph Domain In Tec Family Kinasesmentioning

confidence: 99%

Tec Kinase Signaling in T Cells Is Regulated by Phosphatidylinositol 3-Kinase and the Tec Pleckstrin Homology Domain

Yang

Ching

Tsoukas

et al. 2001

The Journal of Immunology

View full text Add to dashboard Cite

Tec, the prototypical member of the Tec family of tyrosine kinases, is abundantly expressed in T cells and other hemopoietic cell types. Although the functions of Itk and Txk have recently been investigated, little is known about the role of Tec in T cells. Using antisense oligonucleotide treatment to deplete Tec protein from primary T cells, we demonstrate that Tec plays a role in TCR signaling leading to IL-2 gene induction. Interestingly, Tec kinases are the only known family of tyrosine kinases containing a pleckstrin homology (PH) domain. Using several PH domain mutants overexpressed in Jurkat T cells, we show that the Tec PH domain is required for Tec-mediated IL-2 gene induction and TCR-mediated Tec tyrosine phosphorylation. Furthermore, we show that Tec colocalizes with the TCR after TCR cross-linking, and that both the Tec PH and Src homology (SH) 2 domains play a role in this association. Wortmannin, a phosphatidylinositol 3-kinase inhibitor, abolishes Tec-mediated IL-2 gene induction and Tec tyrosine phosphorylation, and partially suppresses Tec colocalization with the activated TCR. Thus, our data implicate the Tec kinase PH domain and phosphatidylinositol 3-kinase in Tec signaling downstream of the TCR.

show abstract

“…1A, bottom panels). It is interesting that a mutation in the SH2 domain of the related kinase Btk, analogous to the R265K mutation in Emt/Itk used here, has been shown to disrupt Btk function (21,22).…”

Section: The Emt/itk Sh2 Domain Is Required For the Tcr/cd3-induced Amentioning

confidence: 99%

TCR/CD3-Induced Activation and Binding of Emt/Itk to Linker of Activated T Cell Complexes: Requirement for the Src Homology 2 Domain

Ching

Grasis

Tailor

et al. 2000

The Journal of Immunology

View full text Add to dashboard Cite

Expressed in mast and T cells/inducible T cell tyrosine kinase (Emt/Itk), a Tec family protein tyrosine kinase, is critical for the development and activation of T lymphocytes. The mechanism through which Emt/Itk mediates its effector functions is poorly understood. In this study, we show that the Emt/Itk Src homology 2 (SH2) domain is critical for the transphosphorylation and activation of Emt/Itk catalytic activity that is mediated by TCR/CD3 engagement. Furthermore, we find that the Emt/Itk SH2 domain is essential for the formation of TCR/CD3-inducible Emt/Itk-LAT complexes, whereas the SH3 domain and catalytic activity are not required. The Emt/Itk-linker of activated T cells (LAT) complexes are biologically important because Jurkat T cells with deficient LAT expression (JCaM2) fail to increase Emt/Itk tyrosine phosphorylation upon TCR/CD3 stimulation. Confocal microscopy reveals that in activated cells, LAT complexes colocalize with TCR/CD3. The present data suggest that upon TCR/CD3 engagement, the Emt/Itk SH2 domain mediates the formation of a molecular complex containing Emt/Itk, LAT, and TCR/CD3; this complex is essential for Emt/Itk activation and function.

show abstract

Constitutive membrane association potentiates activation of Bruton tyrosine kinase

Cited by 64 publications

References 52 publications

Signaling network of the Btk family kinases

Signaling network of the Btk family kinases

Tec Kinase Signaling in T Cells Is Regulated by Phosphatidylinositol 3-Kinase and the Tec Pleckstrin Homology Domain

TCR/CD3-Induced Activation and Binding of Emt/Itk to Linker of Activated T Cell Complexes: Requirement for the Src Homology 2 Domain

Contact Info

Product

Resources

About