Calmodulin disrupts plasma membrane localization of farnesylated KRAS4b by sequestering its lipid moiety.

KRAS4b is a small guanosine triphosphatase (GTPase) protein that regulates several signal transduction pathways that underlie cell proliferation, differentiation, and survival. KRAS4b function requires prenylation of its C terminus and recruitment to the plasma membrane, where KRAS4b activates effector proteins including the RAF family of kinases. The Ca-sensing protein calmodulin (CaM) has been suggested to regulate the localization of KRAS4b through direct, Ca-dependent interaction, but how CaM and KRAS4b functionally interact is controversial.

Coordination of a Single Calcium Ion in the EF-hand Maintains the Off State of the Stromal Interaction Molecule Luminal Domain.

Store operated calcium (Ca) entry (SOCE) is the process whereby endoplasmic reticulum (ER) Ca store depletion causes Orai1-composed Ca channels on the plasma membrane (PM) to open, mediating a rise in cytosolic Ca levels. Stromal interaction molecules (STIMs) are the proteins that directly sense ER Ca content and gate Orai1 channels due to store depletion. The trigger for STIM activation is Ca unbinding from the ER lumen-oriented domains, which consist of a nonconserved amino (N) terminal region and EF-hand and sterile α motif (SAM) domains (EF-SAM), highly conserved from humans to Caenorhabditis elegans.