Regulation of Fibroblast Cell Polarity by Src Tyrosine Kinase

Abstract

Src protein tyrosine kinases (SFKs) are a family of nonreceptor tyrosine kinases that are localized beneath the plasma membrane and are activated during cell adhesion, migration, and elongation. Due to their involvement in the activation of signal transduction cascades, SFKs have been suggested to play important roles in the determination of cell polarity during cell extension and elongation. However, the mechanism underlying Src-mediated polarity formation remains unclear. The present study was performed to investigate the mechanisms underlying Src-induced cell polarity formation and cell elongation using Src knockout fibroblasts (SYFs) together with an inhibitor of Src. Normal and Src knockout fibroblasts were also transfected with a wild-type c-Src, dominant negative c-Src, or constitutively active c-Src gene to analyze the changes in cell morphology. SYF cells cultured on a glass substrate elongated symmetrically into spindle-shaped cells, with the formation of focal adhesions at both ends of the cells. When normal fibroblasts were treated with Src Inhibitor No. 5, a selective inhibitor of Src tyrosine kinases, they elongated into symmetrical spindle-shaped cells, similar to SYF cells. These results suggest that cell polarity during extension and elongation may be regulated by SFKs and that the expression and regulation of Src are important for the formation of polarity during cell elongation.

Plectin promotes tumor formation by B16 mouse melanoma cells via regulation of Rous sarcoma oncogene activity

“…1D). Spindle-shaped cells with thick, long actin fibers and abnormal cell spreading are characteristic of disturbed Src signaling [29]. Consistent with abnormal Src activity in PKO cells, we observed that PKO cells were elongated and less round than control cells (Fig.…”

“…Slides were imaged using a BZ-X810 microscope (Keyence, Osaka, Japan) and analyzed using ImageJ software (NIH). Cells with a maximum diameter more than 5 times greater than their minor diameter were defined as "elongated cells" [29].…”

Effects of Electrical Stimulation on the Signal Transduction-Related Proteins, c-Src and Focal Adhesion Kinase, in Fibroblasts

“…The Src family tyrosine kinases (SFKs) are a family of membrane-associated, non-receptor-type protein tyrosine kinases that have a number of roles in cell-matrix and cell-cell adhesion and are found in endosomal vesicles. Src mediates signal transduction via a variety of receptors [22,23], and activated Src has been shown to induce cell transformation in vitro [24][25][26]. Phosphorylation of FAK at Y397 promotes the formation of the FAK-Src complex.…”

FAK in Cancer: From Mechanisms to Therapeutic Strategies

“…FAK acts as a central hub to fine-tune these cellular processes [31,95,96]. The principal mechanisms through which FAK governs cancer cell adhesion and migration through the formation of the focal adhesion complex and cytoskeleton remodeling (Figure 2) include: (i) functional interactions with Src family kinases [97][98][99][100][101]; (ii) the recruitment of talin to nascent focal adhesions complexes [102,103]; (iii) the formation of p130Cas/Cas/Crk complex [104][105][106]; (iv) functional interactions with small G proteins, such as Ras homolog family member A (RhoA), Rac family small GTPase 1 (Rac1), and cell division cycle 42 (cdc42), to regulate actin cytoskeleton reorganization [107][108][109][110][111][112]. Of actin remodeling, the FAK functionally interacts actin nucleation and elongation factors, such as cortactin, neural Wiskott-Aldrich syndrome protein (N-WASP), and the actin related protein 2/3 (Arp2/3) complex, respectively, with its PRR and FERM domain [113][114][115][116][117].…”