Regulation of protein phosphatase 2A-mediated recruitment of IQGAP1 to β1 integrin by EGF through activation of Ca2+/calmodulin-dependent protein kinase II

Maintenance of 01 integrin-mediated cell adhesion in quiescent human mammary epithelial (HME) cells requires protein phosphatase (PP) 2A for not only dephosphorylation of beta 1 integrin but also recruitment of IQGAP1 to Rac-bound beta 1 integrin. However, how PP2A-dependent regulatory machinery of cell adhesion responds to EGF remains to be elucidated. We report here that phosphorylated Ca2+/calmodulin-dependent protein kinase II(CaMKII) at threonine 286 was involved in the beta 1 integrin complex that consisted of PP2A, Rac, and IQGAP1 in quiescent HME cells. Stimulation of the cells with EGF concomitantly induced an increase in intracellular Ca2+, activation of CaMKII, and dissociation of PP2A-IQGAP1-CaMKII from beta 1 integrin-Rac. Because the activation of CaMKII and dissociation of PP2A-IQGAP1-CaMKII were blocked by either Ca2+-chelator or CaMKII inhibitor, we therefore propose that EGF has the ability to abrogate the PP2A function in the maintenance of P1 integrin-mediated cell adhesion by dissociation of PP2A-IQGAP1-CaMKII from beta 1 integrin-Rac through activation of CaMKII.