title: The kinase c-Src and the phosphatase TC45 coordinately regulate c-Fos tyrosine phosphorylation and c-Fos phospholipid synthesis activation capacity.
abstract: Our previous work showed that in T98G cells, a human glioblastoma multiforme-derived cell line, the association of c-Fos to the endoplasmic reticulum (ER) and consequently, the capacity of c-Fos to activate phospholipid synthesis, is regulated by the phosphorylation state of tyrosine (tyr) residues #10 and #30 of c-Fos. The small amount of c-Fos present in quiescent cells is tyr-phosphorylated, is dissociated from the ER membranes and does not activate phospholipid synthesis. However, on induction of the cell to re-enter growth, c-Fos expression is rapidly induced, it is found dephosphorylated, associated to ER membranes and activating phospholipid synthesis (Portal et al., 2007). Herein, using in vivo and in vitro experimental strategies, we show that the kinase c-Src is capable of phosphorylating tyr residues of c-Fos whereas the phosphatase TC45 T-cell protein-tyr phosphatase (TC-PTP) dephosphorylates them, thus enabling c-Fos/ER association and activation of phospholipid synthesis. Results also suggest that the regulation of the phosphorylation/dephosphorylation cycle of c-Fos occurs at the TC-PTP level: induction of cells to re-enter growth promotes the translocation of TC45 from a nuclear to a cytoplasmic location concomitant with its activation. Activated TC45 in its turn promotes dephosphorylation of pre-formed c-Fos, enabling cells to rapidly activate phospholipid synthesis to respond to its growth demands.
authors: CIQUIBIC (CONICET), Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors: G O
authors: GO
authors: Ferrero
authors: F N
authors: FN
authors: Velazquez
authors: B L
authors: BL
authors: Caputto
mesh_terms: D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007425:Intracellular Membranes / Q000201:enzymology / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D041681:NIH 3T3 Cells; D010743:Phospholipids / Q000096:biosynthesis*; D010766:Phosphorylation; D021381:Protein Transport; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2 / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000737:chemistry* / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*; D019061:src-Family Kinases
chemical_list: D010743:Phospholipids; D016760:Proto-Oncogene Proteins c-fos; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2