Abstract:
:Activins and other members of the transforming growth factor beta family play a critical role in morphological changes of the epidermis that require epithelial cell movement. We investigated the molecular pathways in the transmission of activin signals that lead to actin reorganization and epithelial cell migration. We found that activins cause the activation of RhoA but not of Rac and CDC42, leading to MEKK1-dependent phosphorylation of JNK and transcription factor c-Jun. Through a RhoA-independent mechanism, the activins also induce p38 activity in keratinocytes from wild-type but not from MEKK1-deficient mice. Although neither pathway is dependent on Smad activation, the MEKK1-mediated JNK and p38 activities are both essential for activin-stimulated and transcription-dependent keratinocyte migration. Only JNK is involved in transcription-independent actin stress fiber formation, which needs also the activity of ROCK. Because ROCK is required for JNK activation by RhoA and its overexpression leads to MEKK1 activation, we propose a RhoA-ROCK-MEKK1-JNK pathway and a MEKK1-p38 pathway as Smad-independent mechanisms in the transmission of activin signals. Together, these pathways lead to the control of actin cytoskeleton reorganization and epithelial cell migration, contributing to the physiologic and pathological effects of activins on epithelial morphogenesis.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Zhang L,Deng M,Parthasarathy R,Wang L,Mongan M,Molkentin JD,Zheng Y,Xia Ydoi
10.1128/MCB.25.1.60-65.2005subject
Has Abstractpub_date
2005-01-01 00:00:00pages
60-5issue
1eissn
0270-7306issn
1098-5549pii
25/1/60journal_volume
25pub_type
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