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Volume 271, Number 52, Issue of December 27, 1996 pp. 33525-33530
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

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Molecular Interaction between Limb Deformity Proteins (Formins) and Src Family Kinases

(Received for publication, August 28, 1996)

From the EMBL, Meyerhofstrasse 1, 69117 Heidelberg, Germany

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.

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