Role of Sam68 as an adaptor protein in signal transduction.
Sam68, the substrate of Src in mitosis, belongs to the family of RNA binding proteins. Sam68 contains consensus sequences to interact with other proteins via specific domains. Thus, Sam68 has various proline-rich sequences to interact with SH3 domain-containing proteins. Moreover, Sam68 also has a C-terminal domain rich in tyrosine residues that is a substrate for tyrosine kinases. Tyrosine phosphorylation of Sam68 promotes its interaction with SH2 containing proteins. The association of Sam68 with SH3 domain-containing proteins, and its tyrosine phosphorylation may negatively regulate its RNA binding activity. The presence of these consensus sequences to interact with different domains allows this protein to participate in signal transduction pathways triggered by tyrosine kinases. Thus, Sam68 participates in the signaling of T cell receptors, leptin and insulin receptors. In these systems Sam68 is tyrosine phosphorylated and recruited to specific signaling complexes. The participation of Sam68 in signaling suggests that it may function as an adaptor molecule, working as a dock to recruit other signaling molecules. Finally, the connection between this role of Sam68 in protein-protein interaction with RNA binding activity may connect signal transduction of tyrosine kinases with the regulation of RNA metabolism.
Najib
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Department of Medical Biochemistry and Molecular Biology, School of Medicine, Investigation Unit, Virgen Macarena University Hospital, Av. Sanchez Pizjuan 4, Seville 41009, Spain.
Martín-Romero
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González-Yanes
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Sánchez-Margalet
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D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D004268:DNA-Binding Proteins; D006801:Humans; D011487:Protein Conformation; D012313:RNA / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000502:physiology*; D011972:Receptor, Insulin / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology; D054411:Receptors, Leptin; D015398:Signal Transduction / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C489559:KHDRBS1 protein, human; D016601:RNA-Binding Proteins; D011948:Receptors, Antigen, T-Cell; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D012313:RNA; D011972:Receptor, Insulin