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

Sam68, the 68-kDa S rc substrate a ssociated during m itosis, is an RNA-binding protein with signaling properties that contains a GSG ( G RP33, S am68, G LD-1) domain. Here we report the cloning of two S am68- l ike- m ammalian 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.