ArgBP2, a Multiple Src Homology 3 Domain-containing, Arg/Abl-interacting Protein, Is Phosphorylated in v-Abl-transformed Cells and Localized in Stress Fibers and Cardiocyte Z-disks

Abstract

Arg and c-Abl represent the mammalian members of the Abelson family of protein-tyrosine kinases. A novel Arg/Abl-binding protein, ArgBP2, was isolated using a segment of the Arg COOH-terminal domain as bait in the yeast two-hybrid system. ArgBP2 contains three COOHterminal Src homology 3 domains, a serine/threoninerich domain, and several potential Abl phosphorylation sites. ArgBP2 associates with and is a substrate of Arg and v-Abl, and is phosphorylated on tyrosine in v-Abltransformed cells. ArgBP2 is widely expressed in human tissues and extremely abundant in heart. In epithelial cells ArgBP2 is located in stress fibers and the nucleus, similar to the reported localization of c-Abl. In cardiac muscle cells ArgBP2 is located in the Z-disks of sarcomeres. These observations suggest that ArgBP2 functions as an adapter protein to assemble signaling complexes in stress fibers, and that ArgBP2 is a potential link between Abl family kinases and the actin cytoskeleton. In addition, the localization of ArgBP2 to Z-disks suggests that ArgBP2 may influence the contractile or elastic properties of cardiac sarcomeres and that the Z-disk is a target of signal transduction cascades.

Extracellular Signal-regulated Kinase Activated by Epidermal Growth Factor and Cell Adhesion Interacts with and Phosphorylates Vinexin

“…Vinexin belongs to a novel protein family, which consists of vinexin, c-Cbl-associated protein (CAP)/ponsin, and Arg-binding protein 2 (ArgBP2) (19,(42)(43)(44). These proteins share one sorbin homology domain in the N-terminal region and three SH3 domains in the C-terminal region.…”

Inhibition of Cell Migration by Abl Family Tyrosine Kinases through Uncoupling of Crk-CAS Complexes

“…Recent evidence suggests that Abl family kinases regulate the actin cytoskeleton and influence cell morphology (2)(3)(4)(5)(6)(7)(8). However, the biological significance of this is not clear.…”

“…Coordination of simultaneous binding of Abl to G-and F-actin is thought to aid in the bundling of actin filaments (13). The cytoskeletal-associated proteins, amphiphysin-like protein 1 (ALP1) and Abl/ Arg-binding protein 2 (ArgBP2), also bind Abl family enzymes (5,6), providing a mechanism of indirect interaction between Abl family kinases and the cytoskeleton. In addition, fusion of Bcr to Abl creates Bcr-Abl, which primarily localizes to the cytoskeleton in the cytoplasm and is strongly associated with cell transformation and leukemia (14,15).…”

Quantitative proteomic analysis of S-nitrosated proteins in diabetic mouse liver with ICAT switch method

“…With this quantitative proteomic method, we were able to find a number of new S-nitrosated targets that are known to be involved in diabetes and thus merit special investigation. (A) Arg/Abl binding protein (ArgBP2), this multi-adaptor protein interacts with many important proteins in cell signaling (Wang et al, 1997), including Akt (Yuan et al, 2005) and cbl (Soubeyran et al, 2003), which are involved in the insulininduced glucose transport pathway. S-nitrosated ArgBP2 was only detected in KK-Ay mouse liver, suggesting that Snitrosation of this protein may contribute to dysfunction of the glucose transport pathway.…”