Figure 2.

A working model of the signaling mechanisms that mediate the functional roles of TRPM7.

The channel and kinase of TRPM7 are constitutively active in resting cells. In response to various extracellular or cytosolic stress or stimuli, conduction of Mg²⁺ and Ca²⁺ through the TRPM7 channel can be up- or down-regulated. The TRPM7 kinase can phosphorylate itself, as well as cytosolic substrates. The resulting changes in ionic homeostasis and phosphorylation events produce activation or inhibition of the effector molecules in the epidermal growth factor- or other cytokines-induced signaling pathways. These lead to transcription and translation of the cell cycle regulators, senescence-associated genes, and motility mediators. As a consequence, TRPM7 channel-kinase modulates cellular proliferation, survival, differentiation, growth, adhesion, rounding, and migration, which underlie its mediated functions in physiological responses and embryonic development.