Jy. Wei et al., REGULATION OF MITOGEN-ACTIVATED PROTEIN-KINASE ACTIVATION BY THE CYTOPLASMIC DOMAIN OF THE ALPHA(6) INTEGRIN SUBUNIT, The Journal of biological chemistry, 273(10), 1998, pp. 5903-5907
We examined the possibility that the alpha(6A) and alpha(6B) cytoplasm
ic domain variants of the alpha(6) beta(1) integrin differentially act
ivate p42 and p44 mitogen-activated protein (MAP) kinases, P388D1 macr
ophages that express equivalent surface levels of either the alpha(6A)
beta(1) or alpha(6B)beta(1) integrin were used to examine this issue.
Adhesion to laminin-1 mediated by the alpha(6A)beta(1) integrin trigge
red activation of a substantial fraction of total p42 and p44 MAP kina
ses as assessed using a mobility shift assay, immunoblot analysis with
a phosphospecific MAP kinase antibody, and an immune complex kinase a
ssay, In contrast, ligation of the alpha(6B)beta(1) integrin did not t
rigger significant MAP kinase activation, These data were confirmed by
antibody clustering of the alpha(6) beta(1) integrins, Both the alpha
(6A)beta(1) and alpha(6B)beta(1) integrins were capable of activating
the p70 ribosomal S6 kinase and this activation, unlike MAP kinase act
ivation, is dependent on phosphoinositide 3-OH kinase, Activation of M
AP kinase by alpha(6) beta(1) requires both Pas and protein kinase C a
ctivity, A functional correlate for differential activation of MAP kin
ase was provided by the findings that the alpha(6A)beta(1) transfectan
ts migrated significantly better on laminin than the alpha(6B)beta(1)
transfectants and this migration was dependent on MAP kinase activity
based on the use of the MAP kinase kinase (MEK1) inhibitor PD98059, Ou
r findings demonstrate that the alpha(6) beta(1) integrin can activate
MAP kinase, that this activation is regulated by the cytoplasmic doma
in of the alpha(6) subunit, and that it relates to alpha(6) beta(1)-me
diated migration.