Phosphorylation of SHP-2 Regulates Interactions between the Endoplasmic Reticulum and Focal Adhesions to Restrict Interleukin-1-induced Ca2+ Signaling

Kinectin-dependent ER transport supports the focal complex maturation required for chemotaxis in shallow gradients

“…For example, protein-tyrosine phosphatase 1B (PTP1B, also known as PTPN1), an ER-bound protein, promotes focal complex maturation by targeting negative regulatory sites in Src ( phosphorylated tyrosine 529), paxillin and p130Cas (also known as BCAR1) (Burdisso et al, 2013;Hernández et al, 2006). Meanwhile, Ca 2+ release from the ER induced by interleukin 1β treatment promotes focal complex maturation in a SHP-2-dependent manner (Wang et al, 2006). Kinectin is a structural protein (Kumar et al, 1998;Yu et al, 1995) and rather than directly regulating cell adhesions, kinectin indirectly contributes by mediating ER transport to adhesion sites through kinesin-1 and MTs (Ong et al, 2000;Santama et al, 2004;Zhang et al, 2010).…”

Protein-tyrosine Phosphatase-α and Src Functionally Link Focal Adhesions to the Endoplasmic Reticulum to Mediate Interleukin-1-induced Ca2+ Signaling

“…Plating cells on poly-L-lysine coatings restricts focal adhesion formation to fibronectin bead sites in this system (58). Total internal reflection fluorescence microscopy analysis revealed that co-localization of IP 3 R1 with PTP␣ occurred only after IL-1 treatment and only around FN-coated (but not BSA-coated) beads (Fig.…”

“…Functional Interactions between PTP␣ and IP 3 R-Because the tyrosine phosphorylation state of the IP 3 R dictates its Ca 2ϩ conductance (64 -66), we examined the effects of IL-1 and PTP␣ on the phosphorylation state of IP 3 R1, which is the most prominent isoform in fibroblasts (58). For this assay IP 3 R1 was immunoprecipitated from whole cell lysates of PTP␣ ϩ/ϩ and PTP␣ Ϫ/Ϫ murine fibroblasts, as well as genetically modified NIH3T3…”

Paradoxical roles of FAK in tumor cell migration and metastasis

“…46 SHP-2, a non-receptor tyrosine phosphatase, which can be recruited to focal adhesions by interleukin (IL)-1β, promotes the dephosphorylation of FAK, loss of E-cadherin and migration and metastasis of MCF-7 breast cancer cells. 47,48 Protein-tyrosine phosphatase 1B (PTP 1B) was also shown, in cooperation with α-actinin, to disrupt the FAK-Src complex, dephosphorylate FAK Y397, and significantly increase cell migration. 49 Furthermore, the fact that FAK has a negative role in cell migration under some conditions is supported by the following evidence: FAK deficiency promotes v-Src-induced cell migration; 50 expression of Helicobacter pylori CagA reduces the level of FAK tyrosine phosphorylation and results in impaired cell adhesion and increased cell motility, which is associated with the development of gastric adenocarcinoma; 51 and FAK and paxillin inhibit cell migration by negative regulation of Rac1 activity.…”