Angiotensin II, focal adhesion kinase, and PRX1 enhance smooth muscle expression of lipoma preferred partner and its newly identified binding partner palladin to promote cell migration.

Abstract	Lipoma preferred partner (LPP) is a proline rich LIM domain family protein highly expressed at plasma membrane dense bodies and focal adhesions in smooth muscle cells.(1) Using the C-terminus of LPP as bait in a yeast two hybrid system, palladin, an actin-associated protein was identified. The palladin interacting region of LPP was mapped to the first and second LIM domains. The N-terminus of palladin interacted with LPP both in vitro and in vivo, but not solely through its FPLPPP and FPPPP motifs. Like LPP, palladin, is highly expressed in differentiated smooth muscle, colocalized at focal adhesions, at isolated lamellipodia and at dense bodies in smooth muscle tissue. Both LPP and palladin enhanced cell migration and spreading. LPP and palladin expression was markedly decreased, in contrast to vinculin or paxillin, in migration defective focal adhesion kinase null cells, but was restored by expression of the paired-related homeobox gene-1 protein. We have previously shown in focal adhesion kinase null cells, that tetracycline induced expression of focal adhesion kinase upregulated expression of LPP(2) and now show upregulation of palladin, and paired-related homeobox gene-1 protein. The expression of both LPP and palladin, like smooth muscle alpha-actin, was increased by angiotensin II, regulated by actin dynamics, upregulated by myocardin and expressed in the neointima of injured aorta. Overall, the data suggest that the function of LPP and palladin is context dependent, that they play a critical role in cytoskeletal remodeling, respond to signals induced by vascular injury as well as signals that induce smooth muscle cell hypertrophy, such as angiotension II.
Authors	Li Jin, Michael J Kern, Carol A Otey, Brian R Wamhoff, Avril V Somlyo
Journal	Circulation research (Circ Res) Vol. 100 Issue 6 Pg. 817-25 (Mar 30 2007) ISSN: 1524-4571 [Electronic] United States
PMID	17322171 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References	Actins Cytoskeletal Proteins Homeodomain Proteins LIM Domain Proteins LPP protein, human Phosphoproteins Prrx1 protein, mouse palladin protein, mouse Angiotensin II Focal Adhesion Protein-Tyrosine Kinases
Topics	Actins (metabolism) Angiotensin II (pharmacology) Animals Aorta (injuries, metabolism) Blotting, Western Cell Line Cell Movement (physiology) Cytoskeletal Proteins (genetics, metabolism) Disease Models, Animal Focal Adhesion Protein-Tyrosine Kinases (physiology) Focal Adhesions (metabolism) Gene Expression Regulation (drug effects) Gene Transfer Techniques Homeodomain Proteins (physiology) Humans LIM Domain Proteins Mice Muscle, Smooth, Vascular (metabolism) Organ Specificity Phosphoproteins (genetics, metabolism) Protein Structure, Tertiary (physiology) Pseudopodia (metabolism) Rats Rats, Sprague-Dawley Two-Hybrid System Techniques

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