EGFR and Calmodulin Signalling group

LINES OF RESEARCH

Endosomes as signalling platforms

Summary

Besides K-Ras, Rac1 and Cdc42 are CaM binding proteins present in the endosomal compartment. Thus, we are analyzing the role of CaM in the EGFR signalling through H-Ras, K-Ras and Rac1 and the dynamics of actin in this location. Since another location and a very important place of action of Rac1, Cdc42, CaM and PKCδ is the plasma membrane, it is also essential to study the cellular processes activated by EGFR in plasma membrane in which proteins take part. Mainly, we will focus our investigations in endocytosis, mobility, formation of lamellipodia and cellular migration.



EGFR signaling is initiated at the plasma membrane and remains in the endosomes, these signaling platforms can move to different cellular locations, thereby restricting spatial signaling and controlling different processes in the cell. Accordingly, many signaling proteins of EGFR have been detected in endosomes, for example: Shc, Grb2, Sos, Ras and the kinase Raf-1/B-Raf, MEK i ERK1 / 2. The results obtained by our group indicate that CaM is required for activation of Raf-1 by H-Ras in endosomes. On the other hand, K-Ras4B (and most likely Rac1 and Cdc42) are CaM-binding proteins present in the endosomal compartment.

 

We recently demonstrated that activation of EGFR leads to increased levels of K-Ras4B on endosomes. Therefore it is of great interest to ascertain the role of CaM on the regulation of K-Ras, Rac1 and Cdc42 in this location and its impact at the level of plasma membrane. The objective of this project is the study of the regulation of the signalling of EGFR in endosomes by CaM and its implications in different cellular processes.

Figure 2
Figure 2. K-Ras presence on endosomes after EGF stimulation in COS1 cells
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