Abstract LB-513: Abelson Interactor 1 is a novel substrate of protein kinase D2: potential implications in tumor cell migration

Abstract

Abstract Introduction and Objective: The serine/threonine kinases of the protein kinase D family (PKCmu/PKD1, PKD2, PKCnu/PKD3), a subfamily of the CAMK superfamily, have been implicated in regulation of multiple biological processes including proliferation, survival, apoptosis, angiogenesis and motility. The precise mechanisms by which the three PKDs modulate these processes are incompletely understood and require a better knowledge of their signaling context. Methodology and Results: Using the ProtoArray Human Protein Microarray v4.0 (Invitrogen), we identified Abelson interactor 1 (ABI1) as a novel PKD2 substrate. ABI1 was first identified as the downstream target of Abl tyrosine kinase and is an adaptor protein involved in actin reorganization and lamellipodia formation along with WAVE2. In the present study we illustrate that PKD2 interacts and phosphorylates ABI1 in vitro and in vivo at two potential serine residues. The sites were validated using an antibody that specifically identifies the consensus PKD substrate sequence. Furthermore, PKD2-induced phosphorylation of ABI1 destabilized the interaction between ABI1 and WAVE2 and resulted in relocation of both the proteins from plasma membrane to perinuclear region. Consequences of this destabilization and its potential impact on WAVE2 driven actin polymerization and the associated processes are in the process of investigation. Preliminary results also suggest reduced migration velocity and directedness of a tumor cell. Conclusion: In conclusion, our data demonstrate that ABI1 is a novel substrate of PKD2 that might negatively regulate tumor cell migration via terminating a constitutive interaction between ABI1 and WAVE2. *Impact of ABI1-WAVE2 subcomplex destabilization on WAVE2 induced actin polymerization and lamellipodia extension will be presented at the meeting. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-513. doi:1538-7445.AM2012-LB-513