JNK phosphorylates paxillin and regulates cell migration.

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• The c-Jun amino-terminal kinase (JNK) pathway is traditionally linked to inflammation, proliferation, and apoptosis.
• Emerging evidence suggests JNK's involvement in cell migration, notably in Drosophila dorsal closure and via upstream kinases like MAP kinase/ERK kinase kinase 1.

Purpose of the Study:

• To investigate the role of JNK1 in cell migration.
• To identify JNK1 substrates involved in regulating cell movement.
• To elucidate the mechanism by which JNK1 influences cell adhesion dynamics.

Main Methods:

• Utilized fish keratocytes and rat bladder tumour epithelial cells (NBT-II) to study cell migration.
• Employed in vitro and in vivo phosphorylation assays to examine JNK1 activity on paxillin.
• Generated and analyzed cells expressing a serine 178 alanine mutant of paxillin (Pax(S178A)) in migration assays.

Main Results:

• JNK1 is essential for the rapid migration of fish keratocytes and NBT-II cells.
• JNK1 directly phosphorylates serine 178 on the focal adhesion adaptor protein paxillin.
• Pax(S178A) mutant cells displayed impaired migration, forming stable focal adhesions and exhibiting reduced movement compared to wild-type cells.

Conclusions:

• Phosphorylation of paxillin by JNK1 is a critical step for maintaining the transient focal adhesions required for efficient cell migration.
• This finding highlights a novel role for the JNK pathway in regulating cell motility through modulation of adhesion turnover.