Signaling via PINCH: Functions, binding partners and implications in human diseases

Gene. 2016 Dec 5;594(1):10-15. doi: 10.1016/j.gene.2016.08.039. Epub 2016 Aug 30.

Abstract

Particularly interesting new cysteine-histidine-rich protein (PINCH) is a LIM-domain-only adaptor that plays important roles in cytoskeletal organization and extracellular matrix adhesion, migration, proliferation and survival. Mammalian cells have two functional PINCH proteins, PINCH1 and PINCH2. PINCH not only binds to Nck2 and engages in the signaling of growth factor receptors, but also forms a ternary complex with ILK and parvin (IPP complex). Normally, the IPP complex locates to focal adhesions participating in the signaling of integrins and mediating the interaction of cytoskeleton and extracellular matrix (ECM). Accumulative evidence indicates that abnormalities in PINCH signaling are involved in the pathogenesis of important diseases, such as cancers, renal diseases, cardiomyopathy, and HIV. Therefore, clarifying the functions of PINCH and its interactions with key factors is important for better understanding of signaling events both in health and disease.

Keywords: Adhesion; Focal adhesion; ILK; IPP complex; Nck2; PINCH; Protein-protein interaction; Tumor.

Publication types

  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cardiomegaly / genetics
  • Cardiomegaly / metabolism
  • Extracellular Matrix / genetics
  • Extracellular Matrix / metabolism*
  • Focal Adhesions / genetics
  • Focal Adhesions / metabolism*
  • HIV Infections / genetics
  • HIV Infections / metabolism
  • Humans
  • Kidney Diseases / genetics
  • Kidney Diseases / metabolism
  • LIM Domain Proteins / genetics
  • LIM Domain Proteins / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism
  • Signal Transduction*

Substances

  • Adaptor Proteins, Signal Transducing
  • LIM Domain Proteins
  • LIMS1 protein, human
  • LIMS2 protein, human
  • Membrane Proteins
  • Multiprotein Complexes
  • NCK2 protein, human
  • Neoplasm Proteins
  • Oncogene Proteins