title: Molecular dissection of PINCH-1 reveals a mechanism of coupling and uncoupling of cell shape modulation and survival.
abstract: How cells couple and uncouple regulation of cellular processes such as shape change and survival is an important question in molecular cell biology. PINCH-1, a widely expressed protein consisting of five LIM domains and a C-terminal tail, is an essential focal adhesion protein with multiple functions including regulation of the integrin-linked kinase (ILK) level, cell shape, and survival signaling. We show here that the LIM1-mediated interaction with ILK regulates all these three processes. By contrast, the LIM4-mediated interaction with Nck-2, which regulates cell morphology and migration, is not required for the control of the ILK level and survival. Remarkably, a short 15-residue tail C-terminal to LIM5 is required for both cell shape modulation and survival, albeit it is not required for the control of the ILK level. The C-terminal tail not only regulates PINCH-1 localization to focal adhesions but also functions after it localizes there. These findings suggest that PINCH-1 functions as a molecular platform for coupling and uncoupling diverse cellular processes via overlapping but yet distinct domain interactions.
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xu
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Fukuda
authors.forename: You
authors.initials: Y
authors.lastname: Li
authors.forename: Xiliang
authors.initials: X
authors.lastname: Zha
authors.forename: Jun
authors.initials: J
authors.lastname: Qin
authors.forename: Chuanyue
authors.initials: C
authors.lastname: Wu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000595:Amino Acid Sequence; D017209:Apoptosis; D015153:Blotting, Western; D002448:Cell Adhesion; D048430:Cell Shape; D002470:Cell Survival; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D060588:LIM Domain Proteins; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000378:metabolism; D010766:Phosphorylation; D017354:Point Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C088088:LIMS1 protein, human; D008565:Membrane Proteins; C485544:NCK2 protein, human; D015513:Oncogene Proteins; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins; D004247:DNA