The amphiphysin-like protein 1 (ALP1) interacts functionally with the cABL tyrosine kinase and may play a role in cytoskeletal regulation.
cABL is a protooncogene, activated in a subset of human leukemias, whose protein product is a nonreceptor tyrosine kinase of unknown function. cABL has a complex structure that includes several domains and motifs found in proteins implicated in signal transduction pathways. An approach to elucidate cABL function is to identify proteins that interact directly with cABL and that may serve as regulators or effectors of its activity. To this end, a protein-interaction screen of a phage expression library was undertaken to identify proteins that interact with specific domains of cABL. An SH3-domain-containing protein has been identified that interacts with sequences in the cABL carboxyl terminus. The cDNA encoding ALP1 (amphiphysin-like protein 1) was isolated from a 16-day mouse embryo. ALP1 has high homology to BIN1, a recently cloned myc-interacting protein, and also shows significant homology to amphiphysin, a neuronal protein cloned from human and chicken. The amino terminus has homology to two yeast proteins, Rvs167 and Rvs161, which are involved in cell entry into stationary phase and cytoskeletal organization. ALP1 binds cABL in vitro and in vivo. Expression of ALP1 results in morphological transformation of NIH 3T3 fibroblasts in a cABL-dependent manner. The properties of ALP1 suggest that it may be involved in possible cytoskeletal functions of the cABL kinase. Additionally, these results provide further evidence for the importance of the cABL carboxyl terminus and its binding proteins in the regulation of cABL function.
Kadlec
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Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Pendergast
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AM
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006224:Cricetinae; D003599:Cytoskeleton / Q000502:physiology* / Q000648:ultrastructure; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; C109221:Bin1 protein, mouse; D002352:Carrier Proteins; D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; D025521:Tumor Suppressor Proteins; C075637:amphiphysin; D016315:Proto-Oncogene Proteins c-abl