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

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.

Omentin‐regulated proteins combine a pro‐inflammatory phenotype with an anti‐inflammatory counterregulation in human adipocytes: A proteomics analysis

“…LIMS1 has been described to be upregulated by the pro‐inflammatory TNFα . We found that also omentin is able to upregulate LIMS1 in adipocytes.…”

“…We found that also omentin is able to upregulate LIMS1 in adipocytes. One important role of LIMS1 is the regulation of the function of renal tubules suggesting a potential omentin‐ mediated crosstalk with kidneys and diabetes‐associated nephropathy.…”

Focal adhesion proteins Pinch1 and Pinch2 regulate bone homeostasis in mice

“…Mammalian cells have 2 functional PINCH proteins, PINCH1 (LIMS1) and PINCH2 (LIMS2). They are 5 LIM domain-containing proteins that play important roles in cytoskeletal organization and cell-extracellular matrix adhesion, migration, proliferation, and survival (16)(17)(18)(19)(20)(21). Both PINCH1/2 are ubiquitously expressed in most mammalian tissues and organs, including the heart, lung, liver, kidney, and bladder (20).…”

“…They are 5 LIM domain-containing proteins that play important roles in cytoskeletal organization and cell-extracellular matrix adhesion, migration, proliferation, and survival (16)(17)(18)(19)(20)(21). Both PINCH1/2 are ubiquitously expressed in most mammalian tissues and organs, including the heart, lung, liver, kidney, and bladder (20). Global deletion of Pinch1 in mice causes lethality (17), while Pinch2-KO mice have no apparent phenotypes (19,22).…”

Novel functions for integrin-associated proteins revealed by myofibril attachment inDrosophila

“…binding!to!PINCH,!and!the!function!of!this!complex!is!not!well!understood! (Xu!et!al.,!2016).! Here!we!show!that!instead!of!promoting!IPP!function,!as!previously!thought!…”