Polarized distribution of Bcr-Abl in migrating myeloid cells and co-localization of Bcr-Abl and its target proteins

Skourides, Paris A.; Perera, Samanthi A.; Ren, Ruibao

doi:10.1038/sj.onc.1202407

Cited by 31 publications

(35 citation statements)

References 58 publications

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“…Some of the mechanisms involved in detachment of apoptotic cells are common to those controlling tail retraction during polarized migration. BCR-Abl and some of its target proteins showed polarized distribution, co-localizing with F-actin at trailing portions of migratory 32D cells (Skourides et al, 1999). Organized actin is an essential prerequisite for cell constriction and c-Abl regulates polarized actin accumulation by downregulation of Ena (Grevengoed et al, 2003).…”

Section: C3g Is a Target And Effector Of C-abl Functionmentioning

confidence: 98%

F-actin-binding domain of c-Abl regulates localized phosphorylation of C3G: role of C3G in c-Abl-mediated cell death

Mitra

Radha

2010

Oncogene

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Section: C3g Is a Target And Effector Of C-abl Functionmentioning

confidence: 98%

F-actin-binding domain of c-Abl regulates localized phosphorylation of C3G: role of C3G in c-Abl-mediated cell death

Mitra

Radha

2010

Oncogene

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“…Instead, antibodies to ABL or BCR have been used although these detect the normal cellular proteins as well. Studies were conducted by Wetzler et al 22 and Skourides et al 8 which demonstrated that the p210 BCR-ABL /ABL protein is distributed in punctuate structures in the cytoplasm. The study by Wetzler et al 22 analysed the differences between the subcellular distribution of p210 BCR-ABL , normal ABL and normal BCR in various cell lines, and Skourides et al 8 demonstrated a similar cytoplasmic distribution of p210 BCR-ABL / ABL in transfected haemopoietic and fibroblast cells.…”

Section: P210mentioning

confidence: 99%

“…Studies were conducted by Wetzler et al 22 and Skourides et al 8 which demonstrated that the p210 BCR-ABL /ABL protein is distributed in punctuate structures in the cytoplasm. The study by Wetzler et al 22 analysed the differences between the subcellular distribution of p210 BCR-ABL , normal ABL and normal BCR in various cell lines, and Skourides et al 8 demonstrated a similar cytoplasmic distribution of p210 BCR-ABL / ABL in transfected haemopoietic and fibroblast cells. They further showed that p210 BCR-ABL /ABL and adaptor proteins such as growth factor-binding protein (GRB2), src homologous and collagen gene and casitas B-cell lymphoma (CBL) colocalize with p210 BCR-ABL in transfected fibroblast cells.…”

Section: P210mentioning

confidence: 99%

Subcellular distribution of p210BCR-ABL in CML cell lines and primary CD34+ CML cells

et al. 2007

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We analysed the subcellular distribution of p210 BCR-ABL protein using a junction-specific anti-BCR-ABL monoclonal antibody and confocal laser scanning microscopy (CLSM). Our studies have shown that p210 BCR-ABL is arranged in discrete foci in the cytoplasm of cell lines and primary CD34 þ cells but not mononuclear cells suggesting the foci may be a feature of immature chronic myeloid leukaemia cells. We have devised a strategy to score the foci and found the mean number of foci varies between the cell types. The number of foci per cell is directly related to the level of p210 BCR-ABL expression. CLSM was also used to analyse the distribution and colocalization of CT10 regulator-like (CRKL) p210BCR-ABL foci were completely or partially associated, touching or separate in different regions of the same cell. We also analysed the distribution of phosphorylated CRKL (pCRKL) with p210 BCR-ABL and casitas B-cell lymphoma and CRKL but not between p210 BCR-ABL and GRB2. Our observations of the CRKL and p210 BCR-ABL complex may be important for understanding the function of CRKL.

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“…Modulation of c-Abl tyrosine kinase activity has been shown to regulate the actin cytoskeleton in both mammalian cells and during Drosophila axon guidance (7,10,11). Moreover, the Bcr-Abl fusion protein resulting from a reciprocal translocation between the Bcr and c-Abl genes in chronic myelogenous leukemia contains increased intracellular kinase activity and leads to a polarized distribution of the oncoprotein in migrating cells (12). Cell adhesion through integrins also regulates the tyrosine phosphorylation of the cytoskeletal protein paxillin by c-Abl (13).…”

Section: Dok-r Also Known Asmentioning

confidence: 99%

Dok-R Binds c-Abl and Regulates Abl Kinase Activity and Mediates Cytoskeletal Reorganization

Master

Tran

Bishnoi

et al. 2003

Journal of Biological Chemistry

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Dok-R, also known as Dok-2/FRIP, belongs to the DOK family of signaling molecules that become tyrosinephosphorylated by several different receptor and cytoplasmic tyrosine kinases. Tyrosine phosphorylation of DOK proteins establishes high affinity binding sites for other signaling molecules leading to activation of a signaling cascade. Here we show that Dok-R associates with c-Abl directly via a constitutive SH3-mediated interaction and that this binding requires a PMMP motif in the proline-rich tail of Dok-R. The Dok-R-Abl interaction is further enhanced by an active c-Abl kinase, which requires the presence of its SH2 domain. Interaction of Dok-R with c-Abl also results in an increase in c-Abl tyrosine phosphorylation and kinase activity. Furthermore, we demonstrate that this increase in kinase activity correlates with a concomitant increase in c-Ablmediated biological activity as measured by the formation of actin microspikes. Our data are the first to demonstrate that Dok-R and c-Abl interact in both a constitutive and inducible fashion and that Dok-R influences the intracellular kinase and biological activity of c-Abl. Activation of receptor and cytoplasmic tyrosine kinases (TK)1 induces tyrosine phosphorylation of target proteins that initiates a series of protein-protein interactions (1). One of the many targets of TK-mediated signaling pathways is the actin cytoskeleton (2). Actin cytoskeletal rearrangements are important fundamental events that occur during a variety of cellular processes such as adhesion, spreading, migration, proliferation, and differentiation (2). Reorganization of the actin cytoskeleton involves cross-talk between a multitude of different signaling pathways involving kinases, integrins, and other adhesion molecules that target the actin cytoskeletal machinery. Many of these signaling proteins, including the integrin receptors and the cytosolic c-Abl tyrosine kinase, associate directly with the cytoskeleton.Tyrosine phosphorylation of docking and adapter proteins by receptor and cytosolic TKs promotes signal amplification by providing high affinity binding sites for numerous intracellular signaling molecules containing Src homology 2 (SH2) domains or phosphotyrosine binding (PTB) domains. Protein-protein interactions can also occur in a non-inducible manner as seen with the constitutive interaction between Src homology 3 (SH3) domains binding proline-rich motifs. Pleckstrin homology (PH) domains on signaling proteins recognize phospholipids and assist in recruitment of the protein to the plasma membrane. In addition to their role in mediating protein interactions, many of these modular domains found in cytoplasmic TKs also serve to regulate the host kinase.Similar to Src family kinases, c-Abl kinase activity is tightly regulated through intramolecular interactions involving its amino-terminal SH3 domain-containing region (3-5) and can be activated by epidermal and platelet derived growth factors in addition to Src and Src-like kinases (6). c-Abl contains a large array of functional d...

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Polarized distribution of Bcr-Abl in migrating myeloid cells and co-localization of Bcr-Abl and its target proteins

Cited by 31 publications

References 58 publications

F-actin-binding domain of c-Abl regulates localized phosphorylation of C3G: role of C3G in c-Abl-mediated cell death

F-actin-binding domain of c-Abl regulates localized phosphorylation of C3G: role of C3G in c-Abl-mediated cell death

Subcellular distribution of p210BCR-ABL in CML cell lines and primary CD34+ CML cells

Dok-R Binds c-Abl and Regulates Abl Kinase Activity and Mediates Cytoskeletal Reorganization

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