DNA sequence, structure, and tyrosine kinase activity of the Drosophila melanogaster Abelson proto-oncogene homolog.

We report our molecular characterization of the Drosophila melanogaster Abelson gene (abl), a gene in which recessive loss-of-function mutations result in lethality at the pupal stage of development. This essential gene consists of 10 exons extending over 26 kilobase pairs of genomic DNA. The DNA sequence encodes a protein of 1,520 amino acids with strong sequence similarity to the human c-abl proto-oncogene beginning in the type lb 5' exon and extending through the region essential for tyrosine kinase activity. When the tyrosine kinase homologous region was expressed in Escherichia coli, phosphorylation of proteins on tyrosine residues was observed with an antiphosphotyrosine antibody. These results show that the abl gene is highly conserved through evolution and encodes a functional tyrosine protein kinase required for Drosophila development.

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ACK Family Tyrosine Kinase Activity Is a Component of Dcdc42 Signaling during Dorsal Closure in Drosophila melanogaster

Molecular and Cellular Biology ◽

10.1128/mcb.22.11.3685-3697.2002 ◽

2002 ◽

Vol 22 (11) ◽

pp. 3685-3697 ◽

Cited By ~ 15

Author(s):

Kai Ping Sem ◽

Baharak Zahedi ◽

Ivan Tan ◽

Maria Deak ◽

Louis Lim ◽

...

Keyword(s):

Drosophila Melanogaster ◽

Tyrosine Kinase ◽

Kinase Activity ◽

Leading Edge ◽

Small Gtpase ◽

Dominant Negative ◽

Binding Motif ◽

Dorsal Closure ◽

Tyrosine Kinase Activity ◽

Amino Terminal

ABSTRACT We have characterized Drosophila melanogaster ACK (DACK), one of two members of the ACK family of nonreceptor tyrosine kinases in Drosophila. The ACKs are likely effectors for the small GTPase Cdc42, but signaling by these proteins remains poorly defined. ACK family tyrosine kinase activity functions downstream of Drosophila Cdc42 during dorsal closure of the embryo, as overexpression of DACK can rescue the dorsal closure defects caused by dominant-negative Dcdc42. Similar to known participants in dorsal closure, DACK is enriched in the leading edge cells of the advancing epidermis, but it does not signal through activation of the Jun amino-terminal kinase cascade operating in these cells. Transcription of DACK is responsive to changes in Dcdc42 signaling specifically at the leading edge and in the amnioserosa, two tissues involved in dorsal closure. Unlike other members of the ACK family, DACK does not contain a conserved Cdc42-binding motif, and transcriptional regulation may be one route by which Dcdc42 can affect DACK function. Expression of wild-type and kinase-dead DACK transgenes in embryos, and in the developing wing and eye, reveals that ACK family tyrosine kinase activity is involved in a range of developmental events similar to that of Dcdc42.

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Biochemical analysis of torso and D-raf during Drosophila embryogenesis: implications for terminal signal transduction.

Molecular and Cellular Biology ◽

10.1128/mcb.13.2.1163 ◽

1993 ◽

Vol 13 (2) ◽

pp. 1163-1172 ◽

Cited By ~ 29

Author(s):

F Sprenger ◽

M M Trosclair ◽

D K Morrison

Keyword(s):

Signal Transduction ◽

Tyrosine Kinase ◽

Biochemical Analysis ◽

Kinase Activity ◽

Signal Transduction Pathway ◽

Egg Laying ◽

Loss Of Function ◽

Tyrosine Kinase Activity ◽

Phosphorylation State ◽

Drosophila Embryos

Determination of anterior and posterior terminal structures of Drosophila embryos requires activation of two genes encoding putative protein kinases, torso and D-raf. In this study, we demonstrate that Torso has intrinsic tyrosine kinase activity and show that it is transiently tyrosine phosphorylated (activated) at syncytial blastoderm stages. Torso proteins causing a gain-of-function phenotype are constitutively tyrosine phosphorylated, while Torso proteins causing a loss-of-function phenotype lack tyrosine kinase activity. The D-raf gene product, which is required for Torso function, is identified as a 90-kDa protein with intrinsic serine/threonine kinase activity. D-Raf is expressed throughout embryogenesis; however, the phosphorylation state of the protein changes during development. In wild-type embryos, D-Raf is hyperphosphorylated at 1 to 2 h after egg laying, and thereafter only the most highly phosphorylated form is detected. Embryos lacking Torso activity, however, show significant reductions in D-Raf protein expression rather than major alterations in the protein's phosphorylation state. This report provides the first biochemical analysis of the terminal signal transduction pathway in Drosophila embryos.

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Biochemical analysis of torso and D-raf during Drosophila embryogenesis: implications for terminal signal transduction

Molecular and Cellular Biology ◽

10.1128/mcb.13.2.1163-1172.1993 ◽

1993 ◽

Vol 13 (2) ◽

pp. 1163-1172

Author(s):

F Sprenger ◽

M M Trosclair ◽

D K Morrison

Keyword(s):

Signal Transduction ◽

Tyrosine Kinase ◽

Biochemical Analysis ◽

Kinase Activity ◽

Signal Transduction Pathway ◽

Egg Laying ◽

Loss Of Function ◽

Tyrosine Kinase Activity ◽

Phosphorylation State ◽

Drosophila Embryos

Determination of anterior and posterior terminal structures of Drosophila embryos requires activation of two genes encoding putative protein kinases, torso and D-raf. In this study, we demonstrate that Torso has intrinsic tyrosine kinase activity and show that it is transiently tyrosine phosphorylated (activated) at syncytial blastoderm stages. Torso proteins causing a gain-of-function phenotype are constitutively tyrosine phosphorylated, while Torso proteins causing a loss-of-function phenotype lack tyrosine kinase activity. The D-raf gene product, which is required for Torso function, is identified as a 90-kDa protein with intrinsic serine/threonine kinase activity. D-Raf is expressed throughout embryogenesis; however, the phosphorylation state of the protein changes during development. In wild-type embryos, D-Raf is hyperphosphorylated at 1 to 2 h after egg laying, and thereafter only the most highly phosphorylated form is detected. Embryos lacking Torso activity, however, show significant reductions in D-Raf protein expression rather than major alterations in the protein's phosphorylation state. This report provides the first biochemical analysis of the terminal signal transduction pathway in Drosophila embryos.

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