Role of Calcium and Integrin Binding protein 1 (CIB1), a new substrate of PKD2, in tumor growth and angiogenesis

Protein kinase D2 (PKD2) is a member of the PKD family of serine/threonine kinases, a subfamily of the CAMK superfamily. PKDs play a critical role in cell motility, migration and invasion of cancer cells. Expression of PKD isoforms is deregulated in various tumors and our own data show that PKDs play a role in tumor angiogenesis.

In order to further elucidate the role of PKD2 in tumors, we investigated the signaling context of this kinase by performing an extensive substrate screen using an in vitro expression cloning strategy (IVEC). We found that Calcium and Integrin binding protein 1 (CIB1) is a novel in vitro and in vivo substrate of PKD2. CIB1 is a widely distributed protein that has been implicated in angiogenesis, cell migration, and proliferation, all important hallmarks of cancer. Our data show that CIB1, upon phosphorylation by PKD2, stimulates cancer cell invasion and also tumor growth and angiogenesis in the chorioallantois model.

Thus, CIB1 is a novel mediator of PKD-driven carcinogenesis and a potentially interesting therapeutic target.