T. Ng et al., PKC alpha regulates beta 1 integrin-dependent cell motility through association and control of integrin traffic, EMBO J, 18(14), 1999, pp. 3909-3923
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.