title: Syk Is Recruited to Stress Granules and Promotes Their Clearance through Autophagy.
abstract: Syk is a cytoplasmic kinase that serves multiple functions within the immune system to couple receptors for antigens and antigen-antibody complexes to adaptive and innate immune responses. Recent studies have identified additional roles for the kinase in cancer cells, where its expression can either promote or suppress tumor cell growth, depending on the context. Proteomic analyses of Syk-binding proteins identified several interacting partners also found to be recruited to stress granules. We show here that the treatment of cells with inducers of stress granule formation leads to the recruitment of Syk to these protein-RNA complexes. This recruitment requires the phosphorylation of Syk on tyrosine and results in the phosphorylation of proteins at or near the stress granule. Grb7 is identified as a Syk-binding protein involved in the recruitment of Syk to the stress granule. This recruitment promotes the formation of autophagosomes and the clearance of stress granules from the cell once the stress is relieved, enhancing the ability of cells to survive the stress stimulus.
authors.affiliation: From the Department of Medicinal Chemistry and Molecular Pharmacology and the Purdue Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907.
authors.forename: Mariya O
authors.initials: MO
authors.lastname: Krisenko
authors.affiliation: From the Department of Medicinal Chemistry and Molecular Pharmacology and the Purdue Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907.
authors.forename: Reneé L
authors.initials: RL
authors.lastname: Higgins
authors.affiliation: From the Department of Medicinal Chemistry and Molecular Pharmacology and the Purdue Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907.
authors.forename: Soumitra
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: From the Department of Medicinal Chemistry and Molecular Pharmacology and the Purdue Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: From the Department of Medicinal Chemistry and Molecular Pharmacology and the Purdue Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907.
authors.forename: Joy S
authors.initials: JS
authors.lastname: Trybula
authors.affiliation: From the Department of Medicinal Chemistry and Molecular Pharmacology and the Purdue Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907.
authors.forename: Wen-Horng
authors.initials: WH
authors.lastname: Wang
authors.affiliation: From the Department of Medicinal Chemistry and Molecular Pharmacology and the Purdue Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907 geahlen@purdue.edu.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Geahlen
mesh_terms: D018053:Arsenites / Q000494:pharmacology; D001343:Autophagy; D003594:Cytoplasmic Granules / Q000201:enzymology*; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D061986:MCF-7 Cells; D010766:Phosphorylation; D021381:Protein Transport; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000378:metabolism*; D017670:Sodium Compounds / Q000494:pharmacology; D013312:Stress, Physiological; D000072377:Syk Kinase; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism
chemical_list: D018053:Arsenites; D047908:Intracellular Signaling Peptides and Proteins; D017670:Sodium Compounds; D014443:Tyrosine; C017947:sodium arsenite; D012313:RNA; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase
keywords: Grb7; Syk; autophagy; cancer biology; signal transduction; stress granule; tyrosine-protein kinase (tyrosine kinase)