A Drosophila protein-tyrosine phosphatase associates with an adapter protein required for axonal guidance.
We have used the yeast two-hybrid system to isolate a novel Drosophila adapter protein, which interacts with the Drosophila protein-tyrosine phosphatase (PTP) dPTP61F. Absence of this protein in Drosophila causes the mutant photoreceptor axon phenotype dreadlocks (dock) (Garrity, P. A., Rao, Y., Salecker, I., and Zipursky, S. L.(1996) Cell 85, 639-650). Dock is similar to the mammalian oncoprotein Nck and contains three Src homology 3 (SH3) domains and one Src homology 2 (SH2) domain. The interaction of dPTP61F with Dock was confirmed in vivo by immune precipitation experiments. A sequence containing five PXXP motifs from the non-catalytic domain of the PTP is sufficient for interaction with Dock. This suggests that binding to the PTP is mediated by one or more of the SH3 domains of Dock. Immune precipitations of Dock also co-precipitate two tyrosine-phosphorylated proteins having molecular masses of 190 and 145 kDa. Interactions between Dock and these tyrosine-phosphorylated proteins are likely mediated by the Dock SH2 domain. These findings identify potential signal-transducing partners of Dock and propose a role for dPTP61F and the unidentified phosphoproteins in axonal guidance.
Clemens
J C
JC
Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA.
Ursuliak
Z
Z
Clemens
K K
KK
Price
J V
JV
Dixon
J E
JE
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000502:physiology*; D016384:Consensus Sequence; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology*; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D015723:Gene Library; D006801:Humans; D007814:Larva; D008322:Mammals; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D015513:Oncogene Proteins / Q000737:chemistry; D017956:Photoreceptor Cells, Invertebrate / Q000502:physiology; D016133:Polymerase Chain Reaction; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D029721:Drosophila Proteins; C078332:Nck protein; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C099753:dock protein, Drosophila; D017027:Protein Tyrosine Phosphatases