Characterization of Sam68-like mammalian proteins SLM-1 and SLM-2: SLM-1 is a Src substrate during mitosis

Characterization of Sam68-like mammalian proteins SLM-1 and SLM-2: SLM-1 is a Src substrate during mitosis

Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, and Departments of Oncology, Medicine, and Microbiology and Immunology, McGill University, Montréal, PQ H3T 1E2, Canada

Communicated by Philip Leder, Harvard Medical School, Boston, MA (received for review December 29, 1998)

Abstract

Sam68, the 68-kDa Src substrate associated during mitosis, is an RNA-binding protein with signaling properties that contains a GSG (GRP33, Sam68, GLD-1) domain. Here we report the cloning of two Sam68-like-mammalian proteins, SLM-1 and SLM-2. These proteins have an ≈70% sequence identity with Sam68 in their GSG domain. SLM-1 and SLM-2 have the characteristic Sam68 SH2 and SH3 domain binding sites. SLM-1 is an RNA-binding protein that is tyrosine phosphorylated by Src during mitosis. SLM-1 bound the SH2 and SH3 domains of p59^fyn, Grb-2, phospholipase Cγ-1 (PLCγ-1), and/or p120^rasGAP, suggesting it may function as a multifunctional adapter protein for Src during mitosis. SLM-2 is an RNA-binding protein that is not tyrosine phosphorylated by Src or p59^fyn. Moreover, SLM-2 did not associate with the SH3 domains of p59^fyn, Grb-2, PLCγ-1, or p120^rasGAP, suggesting that SLM-2 may not function as an adapter protein for these proteins. The identification of SLM-1 and SLM-2 demonstrates the presence of a Sam68/SLM family whose members have the potential to link signaling pathways with RNA metabolism.

Footnotes

↵ * M.D.F, T.C., and S.R. contributed equally to this work.
↵ † To whom reprint requests should be addressed at: Molecular Oncology Group, Lady Davis Institute, 3755 Côte Ste-Catherine Road, Montréal, PQ H3T 1E2, Canada. e-mail: mcrd{at}musica.mcgill.ca.
Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AF098796 and AF099092).
ABBREVIATIONS:

PLCγ-1,

phospholipase Cγ-1;

EST,

expressed sequence tag;

HA,

hemagglutinin;

GFP,

green fluorescent protein;

GST,

glutathione S-transferase