Lasp-1, a novel type of actin-binding protein accumulating in cell membrane extensions.
The Lasp-1 gene, which has been localized to the q12-q21 region of human chromosome 17, is amplified and overexpressed in human breast cancers. In addition to the previously reported LIM and SH3 domains of Lasp-1, we report here the identification of an actin-binding domain in the core of the protein. This domain is functional as we demonstrate that Lasp-1 binds actin in vivo and in vitro. In addition, confocal analysis of the Lasp-1 subcellular distribution shows that the protein is colocalized with actin at peripheral cell extensions in individual epithelial cancer cells and in transformed fibroblastic cells. Moreover, Lasp-1 is tyrosine phosphorylated in fibroblast cell lines transformed by a constitutively active form of c-Src (c-SrcY527F). Altogether, our results show that Lasp-1 defines a new type of actin-binding protein and suggest that the protein may play a role in a signaling pathway involved in the organization of the cytoskeleton.
Schreiber
V
V
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP Strasbourg, Illkirch, France.
Moog-Lutz
C
C
Régnier
C H
CH
Chenard
M P
MP
Boeuf
H
H
Vonesch
J L
JL
Tomasetto
C
C
Rio
M C
MC
D016475:3T3 Cells; D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D003598:Cytoskeletal Proteins; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D060588:LIM Domain Proteins; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D010766:Phosphorylation; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000235:genetics; D013347:Subcellular Fractions; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D018909:src Homology Domains / Q000235:genetics
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D018398:Homeodomain Proteins; C096353:LASP1 protein, human; D060588:LIM Domain Proteins; C490692:Lasp1 protein, mouse; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D014443:Tyrosine; D016392:Proto-Oncogene Proteins pp60(c-src)