Tyrosine phosphorylation of paxillin and pp125FAK accompanies cell adhesion to extracellular matrix: a role in cytoskeletal assembly.

Abstract

Abstract. Cells in culture reveal high levels of protein tyrosine phosphorylation in their focal adhesions, the regions where cells adhere to the underlying substratum. We have examined the tyrosine phosphorylation of proteins in response to plating cells on extracellular matrix substrata. Rat embryo fibroblasts, mouse Balb/c 3T3, and NIH 3T3 cells plated on fibronectin-coated surfaces revealed elevated phosphotyrosine levels in a cluster of proteins between 115 and 130 kD. This increase in tyrosine phosphorylation was also seen when rat embryo fibroblasts were plated on laminin or vitronectin, but not on polylysine or on uncoated plastic. Integrin mediation of this effect was suggested by finding the same pattern of elevated tyrosine phosphorylation in cells plated on the cell-binding fragment of fibronectin and in ceils plated on a synthetic polymer containing multiple RGD sequences. We have A second protein that becomes tyrosine phosphorylated in response to extracellular matrix adhesion is identified as paxillin, a 70-kD protein previously localized to focal adhesions. Treatment of cells with the tyrosine kinase inhibitor herbimycin A diminished the adhesion-induced tyrosine phosphorylation of these proteins and inhibited the formation of focal adhesions and stress fibers. These results suggest a role for integrin-mediated tyrosine phosphorylation in the organization of the cytoskeleton as cells adhere to the extracellular matrix.

Tyrosine phosphorylation of 100-130 kDa proteins in lung cancer correlates with poor prognosis

“…This kinase was found as a major pTyr-containing protein in RSV-transformed cells and appeared to localise to focal adhesions. Recent studies suggest that pl25FA' kinase is involved in multifanous cellular functions such as cell adhesion (Kornberg et al, 1992), shape (Burridge et al, 1992), motility and growth (Zachary et al, 1992) as well as transformation. Targeting of pl25F gene in mice resulted in a defect of mesoderm development, and cells from these embryos had reduced mobility in vitro (Illic et al, 1995).…”

“…Targeting of pl25F gene in mice resulted in a defect of mesoderm development, and cells from these embryos had reduced mobility in vitro (Illic et al, 1995). pl25F' becomes tyrosine phosphorylated and activated in response to integrin-mediated binding of cells to the extracellular matrix, suggesting pl25FAK phosphorylation is important for cell adhesion and/or migration (Kornberg et al, 1992;Burridge et al, 1992). f-catenin is one of the components of the cadherin-catenin cell adhesion system and appears to play a crucial role in cadherin-dependent cell adhesion.…”

Possible role of protein kinase C in the regulation of intracellular stability of focal adhesion kinase in mouse 3T3 cells

“…Phosphorylation of tyrosine residues of FAK is stimulated in the cells transformed by pp60 ..... , or by attachment of cells to fibronectin or other celladhesive proteins [1][2][3][4][5][6]. Tyrosine kinase activity of FAK is regulated, at least in part, by the phosphorylation of tyrosine residues of FAK [7].…”

An invasion-related complex of cortactin, paxillin and PKCμ associates with invadopodia at sites of extracellular matrix degradation

“…Paxillin, a focal adhesion protein (Turner et al, 1990), is phosphorylated in response to integrinmediated adhesion (Burridge et al, 1992). V-Src transformation causes a partial redistribution of paxillin from focal adhesions to invadopodia in Rous sarcoma virus-transformed chicken embryo ®broblasts grown on a gelatin matrix (Mueller et al, 1992).…”