Connector Enhancer of Kinase Suppressor of Ras 1 Proteins (CNKSR1)

Human Connector Enhancer of Kinase Suppressor of Ras 1 (CNKSR1) interaction partners

1. CNKSR1 expression is increased in pancreatic cancer specimens and was found to be an independent prognostic marker of overall survival.

2. Data indicate connector enhancer of kinase suppressor of Ras 1 protein (CNK1) as a molecular platform that controls c-raf protein (RAF) and c-akt protein (AKT) signalling and determines cell fate decisions in a cell type- and cell stage-dependent manner.

3. The findings reveal SAM domain-dependent oligomerization by AKT as a switch for CNK1 activation.

4. tyrosine phosphorylation is an important mechanism to control the subcellular localization of CNK1 and its distinct biological functions.

5. CNK1 mediates ephrinB1 signaling that promotes cell migration through RhoA and JNK activity.

6. Studies indicate that CNK1-driven proliferation relies on Akt-dependent phosphorylation and inactivation of FoxO proteins.

7. These findings identify CNK1 as a new positive regulator of insulin signaling.

8. Thus, CNK1 is an essential mediator of an oncogenic pathway involved in invasion of breast and cervical cancer cells and is therefore a putative target for cancer therapy.

9. CNK1 promotes oncogenic signalling through Akt in breast cancer cell lines and tumours.

10. hCNK1 associates with Rhophilin and RalGDS, Rho and Ras effector molecules, respectively, suggesting that it acts as a scaffold protein to mediate cross talk between the two pathways

11. Data show that the connector enhancer of KSR 1 scaffold protein, through its binding of a RASSF1A/MST1 complex, participates in the proapoptotic signaling initiated by active Ras.

12. CNK1 couples a subset of Rho exchange factors to activation of the JNK MAP kinase pathway and that signaling specificity is achieved through complexes containing both upstream activators and downstream targets of Rho.

13. CNK1 allows cross-talk between Src and Raf-1 and is essential for the full activation of Raf-1

14. CNK1 binds through the sterile alpha motif (SAM) and the conserved region in CNK (CRIC) to the AT2 receptor. CNK1 may play a role in the AT2 receptor-mediated signaling pathways.

15. DC-SIGN was constitutively associated with a signalosome complex consisting of the scaffold proteins LSP1, KSR1 and CNK and the kinase Raf-1.