PKC alpha regulates beta 1 integrin-dependent cell motility through association and control of integrin traffic

Protein kinase C (PKC) has been implicated in integrin-mediated spreading a nd migration. In mammary epithelial cells there is a partial co-localizatio n between beta 1 integrin and PKC alpha. This reflects complexes between th ese proteins as demonstrated by fluorescense resonance energy transfer (FRE T) monitored by fluorescence lifetime imaging microscopy and also by coprec ipitation. Constitutive complexes are observed for the intact PKC alpha and also form with the regulatory domain in an activation-dependent manner. Ex pression of PKC alpha causes upregulation of beta 1 integrin on the cell su rface, whereas stimulation of PKC induces internalization of beta 1 integri n. The integrin initially traffics to an endosomal compartment in a Ca2+/PI 3-kinase/ dynamin I-dependent manner and subsequently enters an endocytic recycling pathway. This induction of endocytosis by PKC alpha is a function of activity and is not observed for the regulatory domain. PKC alpha, but not PKC alpha regulatory domain expression stimulates migration on beta 1 i ntegrin substrates, This PKC alpha-enhanced migratory response is inhibited by blockade of endocytosis.