title: Identification and functional analysis of a new phosphorylation site (Y398) in the SH3 domain of Abi-1.
abstract: Abi-1 is an adaptor protein for Abelson kinase (c-Abl), and Abi-1 promotes the Abl-mediated phosphorylation of Mammalian Enabled (Mena) by binding both c-Abl and Mena. Here, we identified a new phosphorylation site (Y398) in the SH3 domain of Abi-1, and disruption of Y398, combined with the previously identified phosphorylation site Y213, significantly weakens the binding of Abi-1 to c-Abl. The SH3 domain of Abi-1 and the proline-rich domain of c-Abl are involved in this interaction. Abi-1 phosphorylation at both sites stimulates the phosphorylation of Mena through the activation of c-Abl kinase. The phosphorylation of Abi-1 also plays a role in enhancing the adhesion of Bcr-Abl-transformed leukemic cells.
authors.affiliation: Laboratory of Molecular Oncology, Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0101, Japan.
authors.forename: Mizuho
authors.initials: M
authors.lastname: Sato
authors.forename: Masahiro
authors.initials: M
authors.lastname: Maruoka
authors.forename: Naohiko
authors.initials: N
authors.lastname: Yokota
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kuwano
authors.forename: Akira
authors.initials: A
authors.lastname: Matsui
authors.forename: Mika
authors.initials: M
authors.lastname: Inada
authors.forename: Takuya
authors.initials: T
authors.lastname: Ogawa
authors.forename: Norihiro
authors.initials: N
authors.lastname: Ishida-Kitagawa
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Takeya
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001549:Benzamides; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D016466:CHO Cells; D002448:Cell Adhesion; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D000068877:Imatinib Mesylate; D020014:K562 Cells; D008840:Microfilament Proteins / Q000378:metabolism; D009154:Mutation; D010750:Phosphoproteins / Q000032:analysis / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000032:analysis / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016315:Proto-Oncogene Proteins c-abl / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D053719:Tandem Mass Spectrometry; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism; D018909:src Homology Domains / Q000235:genetics*
chemical_list: C513733:ABI1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D001549:Benzamides; D003598:Cytoskeletal Proteins; C511939:Enah protein, human; D005353:Fibronectins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D019000:Phosphotyrosine; D014443:Tyrosine; D000068877:Imatinib Mesylate; D016315:Proto-Oncogene Proteins c-abl