IQGAP1 - Key Pathways

Key Pathways

‘’’ERK MAPK’’’ The Ras→Raf→MEK→ERK MAPK signaling pathway plays an integral part in the processes of cell proliferation, differentiation, and apoptosis. This pathway is conserved across all eukaryotes.

Various extracellular signals induce the ERK MAPK pathway including EGF, IGF-1, PDGF, and NGF. The various scaffolds of this pathway, including IQGAP1, are responsible for modulating the cellular response to the activity of this pathway. For instance, in a given cell line, activation by one extracellular signal may induce differentiation but not proliferation, while activation of the same ERK MAPK pathway by a different extracellular signal will induce proliferation but not differentiation. IQGAP1 seems to be responsible for the specific output of the pathway upon activation by EGF.

IQGAP1 plays a significant role in the propagation of this MAPK signaling pathway. IQGAP directly binds b-RAF, MEK1/2 and ERK1/2, and is in fact necessary for the phosphorylation (activation) of ERK upon stimulation by EGF.

‘’’Cytoskeletal control (actin dynamics) ‘’’ Actin is a major building block of every eukaryotic cell’s cytoskeleton. Actin dynamics play a major role in cell motility (filaments are built at the leading edge of a moving cell and deconstructed at the receding edge). IQGAP1 binds actin and influences actin dynamics by localizing to the leading edge and recruiting actin polymerization machinery.

IQGAP1 binds and is a target of the Rho GTPases CDC42 and RAC1 which are well known regulators of the actin cytoskeleton. Despite its name, IQGAP1 does not have GAP function, and instead stabilizes active Cdc42. This increase in a local pool of active Cdc42 stimulates actin filament formation and thus filopodia formation.

IQGAP1 can crosslink actin, and in many organisms, IQGAP1 is involved in cytokinesis.