A new link between the c-Abl tyrosine kinase and phosphoinositide signalling through PLC-γ1

Plattner, Rina; Irvin, Brenda J.; Guo, Shuling; Blackburn, Kevin; Kazlauskas, Andrius; Abraham, Robert T.; York, John D.; Pendergast, Ann Marie

doi:10.1038/ncb949

Cited by 124 publications

(164 citation statements)

References 45 publications

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“…Modest elevation of Abl expression can promote cell migration in response to platelet-derived growth factor (Plattner et al, 2003), but Arg does not share this property (Plattner et al, 2004). These data point to clear differences in the regulation of cell migration by Abl and Arg.…”

Section: Do Abl and Arg Play Different Roles In The Regulation Of Celmentioning

confidence: 58%

The Abl-related Gene Tyrosine Kinase Acts through p190RhoGAP to Inhibit Actomyosin Contractility and Regulate Focal Adhesion Dynamics upon Adhesion to Fibronectin

Peacock

Miller

Bradley

et al. 2007

MBoC

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In migrating cells, actin polymerization promotes protrusion of the leading edge, whereas actomyosin contractility powers net cell body translocation. Although they promote F-actin-dependent protrusions of the cell periphery upon adhesion to fibronectin (FN), Abl family kinases inhibit cell migration on FN. We provide evidence here that the Abl-related gene (Arg/Abl2) kinase inhibits fibroblast migration by attenuating actomyosin contractility and regulating focal adhesion dynamics. arg؊/؊ fibroblasts migrate at faster average speeds than wild-type (wt) cells, whereas Arg re-expression in these cells slows migration. Surprisingly, the faster migrating arg؊/؊ fibroblasts have more prominent F-actin stress fibers and focal adhesions and exhibit increased actomyosin contractility relative to wt cells. Interestingly, Arg requires distinct functional domains to inhibit focal adhesions and actomyosin contractility. The kinase domain-containing Arg N-terminal half can act through the RhoA inhibitor p190RhoGAP to attenuate stress fiber formation and cell contractility. However, Arg requires both its kinase activity and its cytoskeleton-binding C-terminal half to fully inhibit focal adhesions. Although focal adhesions do not turn over efficiently in the trailing edge of arg؊/؊ cells, the increased contractility of arg؊/؊ cells tears the adhesions from the substrate, allowing for the faster migration observed in these cells. Together, our data strongly suggest that Arg inhibits cell migration by restricting actomyosin contractility and regulating its coupling to the substrate through focal adhesions.

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Section: Do Abl and Arg Play Different Roles In The Regulation Of Celmentioning

confidence: 58%

The Abl-related Gene Tyrosine Kinase Acts through p190RhoGAP to Inhibit Actomyosin Contractility and Regulate Focal Adhesion Dynamics upon Adhesion to Fibronectin

Peacock

Miller

Bradley

et al. 2007

MBoC

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“…In this system, the association between PLC and INAD is important to terminate the light response via PLC functioning as a GAP. PLC␥ has been shown to bind several kinases including Tnk1, c-Abl, focal adhesion kinase, and TKRs (both EGFR and PDGF receptor) (55,58). However, these interactions result in direct tyrosine phosphorylation of PLC␥.…”

Section: Discussionmentioning

confidence: 99%

GIT1 Mediates Src-dependent Activation of Phospholipase Cγ by Angiotensin II and Epidermal Growth Factor

Haendeler

Yin

Hojo

et al. 2003

Journal of Biological Chemistry

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Critical events for vasoconstrictor and growth factor signal transduction include stimulation of phospholipase C␥ (PLC␥) and elevation of intracellular calcium. c-Src has been proposed as a common mediator for these signals activated by both G protein-coupled receptors (GPCRs) and tyrosine kinase-coupled receptors (TKRs). Here we show that the GPCR kinase-interacting protein-1 (GIT1) is a substrate for c-Src that undergoes tyrosine phosphorylation in response to angiotensin II (AngII) and EGF in vascular smooth muscle and 293 cells. GIT1 associates with PLC␥ via the PLC␥ Src homology 2 and 3 domains constitutively, and the interaction is unaltered by AngII and EGF. GIT1 interaction with PLC␥ is required for PLC␥ activation based on inhibition of tyrosine phosphorylation and calcium mobilization after GIT1 knockdown with antisense GIT1 oligonucleotides. GIT1 interacts with PLC␥ via a novel Spa homology domain (SHD) and a coiled-coil domain. Deletion mutation analysis showed that GIT1(SHD) is required for AngII-and EGF-mediated PLC␥ activation (measured by phosphorylation of Tyr 783 and inositol 1,4,5-trisphosphate formation). We propose that GIT1 is a novel regulator of PLC␥ function that mediates PLC␥ activation by c-Src and integrates signal transduction by GPCRs and TKRs.

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“…If so, this suggests that the c-Abl and SHIP not only propagate their own signals but simultaneously block the alternative pathway. A clue as to how this might occur comes from the finding that PI(4,5)P 2 binds to and inhibits c-Abl kinase activity (18). Indeed, decreasing cellular levels of PI(4,5)P 2 by either phospholipase C␥1-mediated hydrolysis or dephosphorylation by inositol polyphosphate 5-phosphatase results in an increase in c-Abl kinase activity.…”

Section: Discussionmentioning

confidence: 99%

The B Cell Inhibitory Fc Receptor Triggers Apoptosis by a Novel c-Abl Family Kinase-dependent Pathway

Tzeng

Bolland

Inabe

et al. 2005

Journal of Biological Chemistry

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The inhibitory Fc receptors function to regulate the antigendriven activation and expansion of lymphocytes. In B cells, the Fc␥RIIB1 is a potent inhibitor of B cell antigen receptor (BCR) signaling when coligated to the BCR by engagement of antigen-containing immune complexes. Inhibition is mediated by the recruitment of the inositol phosphatase, SHIP, to the Fc␥RIIB1 phosphorylated tyrosine-based inhibitory motif (ITIM). Here we show that BCR-independent aggregation of the Fc␥RIIB1 transduces an ITIM-and SHIP-independent proapoptotic signal that is dependent on members of the c-Abl tyrosine kinase family. These results define a novel Abl family kinase-dependent Fc␥RIIB1 signaling pathway that functions independently of the BCR in controlling antigen-driven B cell responses.B cell antibody responses are initiated by the binding of multivalent antigens to the B cell antigen receptor (BCR) 2 (1, 2). Engagement of the BCR triggers signal cascades that lead to the proliferation of the B cells and their differentiation into both long and short lived antibody-secreting plasma cells and memory B cells. The antigen-driven expansion and differentiation of B cells is a carefully balanced process that ensures adequate levels of circulating protective antibody and memory B cells and simultaneously avoids excessive deleterious production of antibody such as occurs in autoimmune diseases. The low affinity inhibitory receptor for IgG, Fc␥RIIB1, has emerged as a key regulator of B cells responses (3). Although B cells express members of the recently identified extended family of FcR homologs these proteins do not appear to bind Fcs and thus do not function as FcRs (4). During an immune response, once antibody levels reach a critical point resulting in the formation of antigen-and antibody-containing immune complexes (ICs), the simultaneous binding of ICs to the BCR and Fc␥RIIB1 inhibits BCR signaling. Coligation of the Fc␥RIIB1 and the BCR by ICs leads to the phosphorylation of the Fc␥RIIB1 by the Src family kinase Lyn on the tyrosines in the immunoreceptor tyrosine-based inhibitory motif (ITIM), resulting in the recruitment of the inositol phosphatase, SHIP, which inhibits the BCR trigger Ca 2ϩ mobilization and B cell proliferation (3). The inhibition of Ca 2ϩ mobilization and proliferation appears to proceed through two separable pathways, one requiring the phosphatase activity of SHIP to hydrolyze PI3K-generated phosphatidylinositol trisphosphate preventing Btk and phospholipase C␥ activation (5) and a second requiring SHIP to recruit the Ras GAP-binding protein p62 dok that functions to inhibit extracellular signal-regulated kinase activation (6). The physiological significance of the role of the Fc␥RIIB1 in regulating BCR signaling is demonstrated by the phenotype of Fc␥RIIB1-deficient mice that show susceptibility to induced autoimmune diseases and to spontaneous autoimmune disease in certain strains (7).In addition to its inhibitory activity when coligated to the BCR, the Fc␥RIIB1, when aggregated to itself, propagates a...

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A new link between the c-Abl tyrosine kinase and phosphoinositide signalling through PLC-γ1

Cited by 124 publications

References 45 publications

The Abl-related Gene Tyrosine Kinase Acts through p190RhoGAP to Inhibit Actomyosin Contractility and Regulate Focal Adhesion Dynamics upon Adhesion to Fibronectin

The Abl-related Gene Tyrosine Kinase Acts through p190RhoGAP to Inhibit Actomyosin Contractility and Regulate Focal Adhesion Dynamics upon Adhesion to Fibronectin

GIT1 Mediates Src-dependent Activation of Phospholipase Cγ by Angiotensin II and Epidermal Growth Factor

The B Cell Inhibitory Fc Receptor Triggers Apoptosis by a Novel c-Abl Family Kinase-dependent Pathway

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