Featured Review Cellscience Reviews Vol 5 No 1 ISSN 1742-8130

Structural and signaling roles of PINCH in cell-matrix adhesion, migration and survival

PINCH is an evolutionally conserved protein family that plays pivotal roles in regulation of cell-extracellular matrix (ECM) adhesion, shape change, migration and survival. One characteristic structural feature of PINCH proteins is that they contain almost exclusively five tandem LIM domains. The presence of multiple LIM domains allows PINCH to interact with a large number of proteins with diverse affinities. PINCH forms stable ternary complexes with integrin linked kinase (ILK) and parvin in all vertebrate and invertebrate cell types that have been examined. In addition, PINCH interacts with Nck-2, thymosin β4, Ras Suppressor-1 (RSU-1), UNC-98, and several LIM-containing proteins including Hic-5, LIM-8, LIM-9 and UNC-95. The PINCH-ILK-parvin complexes localize to cell-ECM adhesions, where they interact with integrins and multiple actin cytoskeletal proteins and thereby physically link the integrins to the actin cytoskeleton. Additionally, PINCH, together with its binding partners, regulates key signaling intermediates including Akt, JNK and ERK and influence intercellular signaling cascades. Finally, PINCH can shuttle between the cytoplasmic and nuclear compartments and potentially influence nuclear activities. Thus, PINCH is emerging as an important scaffolding protein that plays both structural and signaling roles in the cellular control of cell-ECM adhesion, shape change, migration and survival.

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