title: PTPL1/FAP-1 negatively regulates TRIP6 function in lysophosphatidic acid-induced cell migration.
abstract: The LIM domain-containing TRIP6 (Thyroid Hormone Receptor-interacting Protein 6) is a focal adhesion molecule known to regulate lysophosphatidic acid (LPA)-induced cell migration through interaction with the LPA2 receptor. LPA stimulation targets TRIP6 to the focal adhesion complexes and promotes c-Src-dependent phosphorylation of TRIP6 at Tyr-55, which creates a docking site for the Crk Src homology 2 domain, thereby promoting LPA-induced morphological changes and cell migration. Here we further demonstrate that a switch from c-Src-mediated phosphorylation to PTPL1/Fas-associated phosphatase-1-dependent dephosphorylation serves as an inhibitory feedback control mechanism of TRIP6 function in LPA-induced cell migration. PTPL1 dephosphorylates phosphotyrosine 55 of TRIP6 in vitro and inhibits LPA-induced tyrosine phosphorylation of TRIP6 in cells. This negative regulation requires a direct protein-protein interaction between these two molecules and the phosphatase activity of PTPL1. In contrast to c-Src, PTPL1 prevents TRIP6 turnover at the sites of adhesions. As a result, LPA-induced association of TRIP6 with Crk and the function of TRIP6 to promote LPA-induced morphological changes and cell migration are inhibited by PTPL1. Together, these results reveal a novel mechanism by which PTPL1 phosphatase plays a counteracting role in regulating TRIP6 function in LPA-induced cell migration.
authors.affiliation: Department of Cell Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0005, USA.
authors.forename: Yun-Ju
authors.initials: YJ
authors.lastname: Lai
authors.forename: Weei-Chin
authors.initials: WC
authors.lastname: Lin
authors.forename: Fang-Tsyr
authors.initials: FT
authors.lastname: Lin
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D025461:Feedback, Physiological; D006801:Humans; D060588:LIM Domain Proteins; D008246:Lysophospholipids / Q000502:physiology*; D051379:Mice; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D054645:Protein Phosphatase 1; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D060588:LIM Domain Proteins; D008246:Lysophospholipids; C092282:PSMC5 protein, human; D014157:Transcription Factors; D054645:Protein Phosphatase 1; C516742:PTPN13 protein, human; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases; C516743:Ptpn13 protein, mouse; D046988:Proteasome Endopeptidase Complex; D000074183:ATPases Associated with Diverse Cellular Activities; C032881:lysophosphatidic acid