Functional Mechanisms and Roles of Adaptor Proteins in Abl-Regulated Cytoskeletal Actin Dynamics

Abstract

Abl is a nonreceptor tyrosine kinase and plays an essential role in the modeling and remodeling of F-actin by transducing extracellular signals. Abl and its paralog, Arg, are unique among the tyrosine kinase family in that they contain an unusual extended C-terminal half consisting of multiple functional domains. This structural characteristic may underlie the role of Abl as a mediator of upstream signals to downstream signaling machineries involved in actin dynamics. Indeed, a group of SH3-containing accessory proteins, or adaptor proteins, have been identified that bind to a proline-rich domain of the C-terminal portion of Abl and modulate its kinase activity, substrate recognition, and intracellular localization. Moreover, the existence of signaling cascade and biological outcomes unique to each adaptor protein has been demonstrated. In this paper, we summarize functional roles and mechanisms of adaptor proteins in Abl-regulated actin dynamics, mainly focusing on a family of adaptor proteins, Abi. The mechanism of Abl's activation and downstream signaling mediated by Abi is described in comparison with those by another adaptor protein, Crk.

The adaptor protein Crk in immune response

“…Crk may regulate the F‐actin dynamics via two distinct pathways. One is that Crk interacts with several downstream signal molecules such as Paxillin, C3G/Rap‐1 and p130Cas/DOCK180 (180‐kDa protein downstream of Crk)/Rac‐1 (Ras‐related C3 botulinum toxin substrate 1) to regulate F‐actin 14 . The second pathway could be the interaction between Crk and pVav‐1, as shown in Figure 4.…”

“…Finding the proteins that interact with Crk in normal or transformed fibroblasts has represented a main effort during the past three decades. Several reviews have discussed the physiological and pathological function of Crk, 8 , 10 , 11 signaling complex formation, 7 , 12 roles of Crk in human cancer 13 and roles of Crk in cytoskeletal actin dynamics 14 . Few studies on Crk have discussed the function of Crk in lymphocytes 15 , 16 .…”

Gelsolin Induces Promonocytic Leukemia Differentiation Accompanied by Upregulation of p21CIP1

“…Also, in megakaryoblastic leukaemic cell lines, the expression of scinderin, another actinregulatory protein, induces differentiation, maturation and apoptosis (Bhat et al, 2009). The actin cytoskeleton is an essential scaffold for integrating membrane and intracellular function, whose dynamics are regulated by a number of accessory proteins (Sato, 2012). It has been demonstrated that gelsolin, a ubiquitous protein expressed in almost all mammalian tissues (Kuzumaki and Maruta, 2002), also has an important role in actin reorganization (Furnish, 2001).…”

Abl Tyrosine Kinase Regulates Hepatitis C Virus Entry

“…It has been previously reported that Abl tyrosine kinase is implicated in viral pathogenesis ( Coyne and Bergelson, 2006 ; Sato et al, 2012 ). To investigate the functional involvement of Abl in HCV propagation, Huh7.5 cells transfected with siRNAs were infected with Jc1 (genotype 2a).…”