enabled, a dosage-sensitive suppressor of mutations in the Drosophila Abl tyrosine kinase, encodes an Abl substrate with SH3 domain-binding properties.

Gertler, Frank B.; Comer, Allen R.; Juang, Jyh‐Lyh; Ahern, S; Clark, Michael J.; Liebl, Eric C.; Hoffmann, F. M.

doi:10.1101/gad.9.5.521

Cited by 244 publications

(239 citation statements)

References 52 publications

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“…The results with Bcr-Abl are interesting in light of the fact that Drosophila Abl tyrosine kinase and Ena are proposed to play a role in regulating cytoskeletal changes during axonogenesis (Gertler et al, 1995). Of related interest is the ®nding that in mammalian systems, Bcr-Abl is also observed to alter cytoskeletal function and cell adhesion.…”

Section: Discussionmentioning

confidence: 86%

“…Higher levels of P210 and P185 Bcr-Abl neural expression produced CNS defects reminiscent of that which is seen in ena mutant animals in that longitudinal and commisural axons appeared less tightly bundled and increased numbers of axons exited the CNS from the longitudinal tracts (Gertler et al, 1995). The results with Bcr-Abl are interesting in light of the fact that Drosophila Abl tyrosine kinase and Ena are proposed to play a role in regulating cytoskeletal changes during axonogenesis (Gertler et al, 1995).…”

Section: Discussionmentioning

confidence: 92%

Section: Expression Of Bcr-abl In¯ies Produces Increased Phosphorylatmentioning

confidence: 99%

“…Drosophila Ena functions as a phosphotyrosine substrate for human and Drosophila Abl kinase when co-expressed in cells (Gertler et al, 1995). The observation that abl mutant ies show a two-to threefold decrease in Ena phosphotyrosine content suggests that Ena also functions as an Abl phosphotyrosine substrate in vivo (Gertler et al, 1995). We looked at whether endogenous Ena tyrosine phosphorylation is increased in animals expressing Bcr-Abl under the control of the Figure 6 Eye imaginal discs from transformants expressing P210 Bcr-Abl, P185 Bcr-Abl and Drosophila Abl targeted by sev-GAL4.…”

Section: Expression Of Bcr-abl In¯ies Produces Increased Phosphorylatmentioning

confidence: 99%

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Dominant effects of the bcr-abl oncogene on Drosophila morphogenesis

Petersen

et al. 1999

Oncogene

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We targeted expression of human/¯y chimeric Bcr-Abl proteins to the developing central nervous system (CNS) and eye imaginal disc of Drosophila melanogaster. Neural expression of human/¯y chimeric P210 Bcr-Abl or P185 Bcr-Abl rescued abl mutant¯ies from pupal lethality, indicating that P210 and P185 Bcr-Abl can substitute functionally for Drosophila Abl during axonogenesis. However, increased levels of neurally expressed P210 or P185 Bcr-Abl but not Drosophila Abl produced CNS defects and lethality. Expression of P210 or P185 in the eye imaginal disc produced a dominant rough eye phenotype that was dependent on dosage of the transgene. Drosophila Enabled, previously identi®ed as a suppressor of the abl mutant phenotype and substrate for Drosophila Abl kinase, had markedly increased phosphotyrosine levels in Bcr-Abl expressing Drosophila, indicating that it is a substrate for Bcr-Abl as well. Drosophila, therefore, is a suitable model system to identify Bcr-Abl interactions important for signal transduction and oncogenesis.

show abstract

Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 92%

Section: Expression Of Bcr-abl In¯ies Produces Increased Phosphorylatmentioning

confidence: 99%

Section: Expression Of Bcr-abl In¯ies Produces Increased Phosphorylatmentioning

confidence: 99%

See 2 more Smart Citations

Dominant effects of the bcr-abl oncogene on Drosophila morphogenesis

Petersen

et al. 1999

Oncogene

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“…Thus, the c-Abl SH3 domain may exert both positive and negative e ects on its catalytic domain. Moreover in Drosophila positive regulation of Abl protein, namely recognition of its substrate Ena, was mediated by its SH3 domain (Gertler et al, 1995). This dual role of the SH3 domain may o er a mechanism that is highly sensitive to signals and extremely selective for substrates.…”

Section: Discussionmentioning

confidence: 99%

The kinase activity of c-Abl but not v-Abl is potentiated by direct interaction with RFXI, a protein that binds the enhancers of several viruses and cell-cycle regulated genes

Agami

Shaul

1998

Oncogene

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c-Abl, the non-receptor tyrosine kinase is associated with EP, a DNA element found in promoters/enhancers of di erent viruses and cell-cycle regulated genes. EP-DNA binds RFXI, a member of a novel family of DNA-binding proteins that is conserved through evolution and in yeast, it controls di erentiation and exit from the mitotic cycle to G 0 . EP-associated proteins are preferentially tyrosine phosphorylated and the associated c-Abl has strong tyrosine kinase activity. Here we investigated the molecular mechanism underlying this c-Abl kinase activity. We show that RFXI and c-Abl are in direct interaction, in vitro and in cell extracts, through the RFXI proline rich (PxxP) motif and the c-Abl SH3 domain. Remarkably, this interaction signi®cantly potentiates cAbl but not v-Abl auto-kinase activity. Collectively, we describe a novel mechanism of c-Abl recruitment to a de®ned DNA-cis element with its concomitant kinase activation. We propose that this mechanism may act to regulate cell-cycle control genes.

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Recruitment of the Arp2/3 complex and Mena for the stimulation of actin polymerization in growth cones by nerve growth factor

et al. 2000

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The growth of axons and dendrites during development and regeneration is regulated by cues in the environment. Many of these cues regulate the actin cytoskeleton of the protrusive structures (like filopodia) of the growth cone that are essential for detecting and responding to cues. Nerve growth factor, which promotes the formation of protrusive structures, stimulated actin polymerization in rat sympathetic growth cones, resulting within 1-2 min in accumulations of F-actin at the distal edge and in splotches of F-actin farther back. We examined the potential involvement of a protein machinery important in at least certain types of actin polymerization in non-neuronal cells. Members of the Arp2/3 complex, p34-Arc and p21-Arc, heavily concentrated in the early accumulations of F-actin, as did one member of the Ena/VASP family (Mena) but not another (VASP). Retention of Arc proteins at preferred sites of actin polymerization did not require polymerization itself. Growth cones of differentiated PC12 cells were similar to sympathetic growth cones in their response to NGF. Introduction into these cells of a peptide that should block the binding of Ena/VASP family proteins to the protein complex at sites of actin polymerization reduced the formation of splotches and filopodia in response to NGF. These results point to the early involvement of the Arp2/3 complex and the Ena/VASP family in growth factor-stimulated actin polymerization that gives rise to protrusive structures at the growth cone.

show abstract

enabled, a dosage-sensitive suppressor of mutations in the Drosophila Abl tyrosine kinase, encodes an Abl substrate with SH3 domain-binding properties.

Cited by 244 publications

References 52 publications

Dominant effects of the bcr-abl oncogene on Drosophila morphogenesis

Dominant effects of the bcr-abl oncogene on Drosophila morphogenesis

The kinase activity of c-Abl but not v-Abl is potentiated by direct interaction with RFXI, a protein that binds the enhancers of several viruses and cell-cycle regulated genes

Recruitment of the Arp2/3 complex and Mena for the stimulation of actin polymerization in growth cones by nerve growth factor

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