5WI4

CRYSTAL STRUCTURE OF DYNLT1/TCTEX-1 IN COMPLEX WITH ARHGEF2

Summary for 5WI4

• Entry DOI: 10.2210/pdb5wi4/pdb
• Descriptor: Dynein light chain Tctex-type 1,Rho guanine nucleotide exchange factor 2, SULFATE ION (3 entities in total)
• Functional Keywords: dynein light chain, rho gef, motor protein, cargo transport
• Biological source: Mus musculus (Mouse); More
• Cellular location: Cytoplasm, cytoskeleton : Q60875
• Total number of polymer chains: 3
• Total formula weight: 47392.55

Authors

Balan, M.,Ishiyama, N.,Marshall, C.B.,Ikura, M. (deposition date: 2017-07-18, release date: 2017-11-15, Last modification date: 2023-10-04)

Primary citation

Sandi, M.J.,Marshall, C.B.,Balan, M.,Coyaud, E.,Zhou, M.,Monson, D.M.,Ishiyama, N.,Chandrakumar, A.A.,La Rose, J.,Couzens, A.L.,Gingras, A.C.,Raught, B.,Xu, W.,Ikura, M.,Morrison, D.K.,Rottapel, R.
MARK3-mediated phosphorylation of ARHGEF2 couples microtubules to the actin cytoskeleton to establish cell polarity.
Sci Signal, 10:-, 2017

PubMed Abstract: The PAR-1-MARK pathway controls cell polarity through the phosphorylation of microtubule-associated proteins. Rho-Rac guanine nucleotide exchange factor 2 (ARHGEF2), which activates Ras homolog family member A (RHOA), is anchored to the microtubule network and sequestered in an inhibited state through binding to dynein light chain Tctex-1 type 1 (DYNLT1). We showed in mammalian cells that liver kinase B1 (LKB1) activated the microtubule affinity-regulating kinase 3 (MARK3), which in turn phosphorylated ARHGEF2 at Ser This modification disrupted the interaction between ARHGEF2 and DYNLT1 by generating a 14-3-3 binding site in ARHGEF2, thus causing ARHGEF2 to dissociate from microtubules. Phosphorylation of ARHGEF2 by MARK3 stimulated RHOA activation and the formation of stress fibers and focal adhesions, and was required for organized cellular architecture in three-dimensional culture. Protein phosphatase 2A (PP2A) dephosphorylated Ser in ARHGEF2 to restore the inhibited state. Thus, we have identified a regulatory switch controlled by MARK3 that couples microtubules to the actin cytoskeleton to establish epithelial cell polarity through ARHGEF2.

PubMed: 29089450
DOI: 10.1126/scisignal.aan3286

Experimental method

X-RAY DIFFRACTION (2 Å)