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 e mbryonic 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-i mmunoprecipitation of Ld and c-Src proteins from transfected cells sho ws that these proteins associate in vivo. Immunolocalization and bioch emical fractionation of fibroblasts confirms the predominant nuclear l ocalization of Ld proteins, but unexpectedly identifies a population o f 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 morp horegulatory Ld proteins interact with signal transduction cascades by association to membrane-bound Src family kinases.