Molecular interaction between limb deformity proteins (formins) and Src family kinases.
Ld proteins (formins) are encoded by the limb deformity (ld) gene and define a family of related gene products regulating establishment of embryonic polarity. In this study we establish that chicken and murine Ld proteins interact directly with Src family kinases (c-Src and c-Fyn). Specific binding is mediated by the proline-rich domain present in Ld proteins and the ligand binding surface of the Src SH3 domain. Co-immunoprecipitation of Ld and c-Src proteins from transfected cells shows that these proteins associate in vivo. Immunolocalization and biochemical fractionation of fibroblasts confirms the predominant nuclear localization of Ld proteins, but unexpectedly identifies a population of Ld proteins associated to cellular membranes. This population of Ld proteins co-localizes with membrane-associated c-Src proteins at both plasma and perinuclear membranes. These studies indicate that the morphoregulatory Ld proteins interact with signal transduction cascades by association to membrane-bound Src family kinases.
Uetz
P
P
EMBL, Meyerhofstrasse 1, 69117 Heidelberg, Germany. Zeller@EMBL-Heidelberg.de
Fumagalli
S
S
James
D
D
Zeller
R
R
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002645:Chickens; D005326:Fetal Proteins / Q000378:metabolism*; D000080865:Formins; D051379:Mice; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D016415:Sequence Alignment; D014018:Tissue Distribution; D014162:Transfection; D019061:src-Family Kinases / Q000378:metabolism*
D005326:Fetal Proteins; D000080865:Formins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D019061:src-Family Kinases