Search results for "Integrin-linked kinase"

2021

The CMS4 mesenchymal subtype of colorectal cancer (CRC) is associated with poor prognosis and resistance to treatment. The cellular prion protein PrPC is overexpressed in CMS4 tumors and controls the expression of a panel of CMS4-specific genes in CRC cell lines. Here, we sought to investigate PrPC downstream pathways that may underlie its role in CMS4 CRC. By combining gene set enrichment analyses and gain and loss of function approaches in CRC cell lines, we identify the integrin-linked kinase ILK as a proximal effector of PrPC that mediates its control on the CMS4 phenotype. We further leveraged three independent large CRC cohorts to assess correlations in gene expression pattern with pa…

Integrin alpha 2 beta 1 promotes activation of protein phosphatase 2A and dephosphorylation of Akt and glycogen synthase kinase 3 beta.

2002

The integrins are a large family of heterodimeric transmembrane receptors composed of α and β subunits (22). In addition to mediating cell-matrix interactions, integrins have been shown to activate intracellular signaling pathways which, in collaboration with growth factor-induced signals, regulate cellular functions (46). Some integrin signaling cascades are activated via the β subunit cytoplasmic domain, and they are therefore triggered by several integrin heterodimers. These signals include the activation of protein tyrosine kinases of the Src and focal adhesion kinase (FAK) families (9, 47). More-recent studies have revealed signaling events that are activated specifically by an α subun…

Profilin 1 is required for peripheral nervous system myelination

2014

Myelination allows rapid saltatory propagation of action potentials along the axon and is an essential prerequisite for the normal functioning of the nervous system. During peripheral nervous system (PNS) development, myelin-forming Schwann cells (SCs) generate radial lamellipodia to sort and ensheath axons. This process requires controlled cytoskeletal remodeling, and we show that SC lamellipodia formation depends on the function of profilin 1 (Pfn1), an actin-binding protein involved in microfilament polymerization. Pfn1 is inhibited upon phosphorylation by ROCK, a downstream effector of the integrin linked kinase pathway. Thus, a dramatic reduction of radial lamellipodia formation is obs…