Regulation of protein phosphatase 2A-mediated recruitment of IQGAP1 to beta1 integrin by EGF through activation of Ca2+/calmodulin-dependent protein kinase II.
Maintenance of beta1 integrin-mediated cell adhesion in quiescent human mammary epithelial (HME) cells requires protein phosphatase (PP) 2A for not only dephosphorylation of beta1 integrin but also recruitment of IQGAP1 to Rac-bound beta1 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 beta1 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 beta1 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 beta1 integrin-mediated cell adhesion by dissociation of PP2A-IQGAP1-CaMKII from beta1 integrin-Rac through activation of CaMKII.
Molecular Cell Biology Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan. ktaka@gancen.asahi.yokohama.jp
Kazuhide
K
Takahashi
Katsuo
K
Suzuki
D002118:Calcium / Q000032:analysis / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000032:analysis / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D019012:Integrin beta1 / Q000032:analysis / Q000502:physiology*; D042361:Mammary Glands, Human / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D010749:Phosphoprotein Phosphatases / Q000032:analysis / Q000502:physiology*; D010766:Phosphorylation; D025941:Protein Interaction Mapping; D054648:Protein Phosphatase 2; D013912:Threonine / Q000032:analysis; D020744:rac GTP-Binding Proteins / Q000032:analysis / Q000502:physiology; D020703:ras GTPase-Activating Proteins / Q000032:analysis / Q000502:physiology*
C101203:IQ motif containing GTPase activating protein 1; D019012:Integrin beta1; D020703:ras GTPase-Activating Proteins; D013912:Threonine; D004815:Epidermal Growth Factor; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D020744:rac GTP-Binding Proteins; D002118:Calcium