Fig 2.

p21-activated kinase (PAK) regulation of Breast Cancer cell actin dynamics. Schematic showing PAK-dependent actin dynamics which promote Breast Cancer cell migration and invasion. (1) Polymerization and stabilization of actin fibres which can be regulated by PAK1 phosphorylation and dephosphorylation, depending on conditions. Also, PAK2 and PAK4 function here. (2) Cell adhesion by stress fibre formation and focal adhesions which counter membrane tension. PAK1 and PAK2 are linked to focal adhesion formation, whereas PAK4 is associated with turnover. (3) Actomyosin contractility is regulated by PAK1 phosphorylating MLCK, and PAK2 dephosphorylating MLCK in order to affect generation of contractile forces. (4) Degradative invasion through invadopodia. The role of PAK1 in invadopodia formation or lifetime is debated, and it is unknown what the role of other PAKs are here. Evidence points towards a role of PAK5 in promoting MMP secretion from invadopodia for ECM degradation. Abbreviations are MLCK = myosin light chain kinase, MMP = matrix metalloproteinase.