TY - JOUR
T1 - Regulation of cytoskeleton organization and paxillin dephosphorylation by cAMP
T2 - Studies on murine Y1 adrenal cells
AU - Han, J. D.
AU - Rubin, C. S.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1996
Y1 - 1996
N2 - Cyclic AMP induces corticosteroid production, differential gene transcription, and cell cycle arrest in adrenal cortex-derived Y1 cells. These responses follow a cAMP-controlled transformation in Y1 cell morphology: the conversion of flat epithelial cells into rounded, highly refractile cells with short processes. Little is known about effector proteins and mechanisms that link activated protein kinase A to the alteration in cell shape. We now report that cAMP causes rapid (≤1 min) and selective tyrosine dephosphorylation of paxillin, a focal adhesion protein. Paxillin is maximally dephosphorylated before other physiological effects of cAMP are detected in Y1 cells. Dephosphopaxillin translocates from focal adhesions to the cytoplasm as stress fibers vanish and F-actin accumulates in membrane ruffles and cytoplasmic aggregates. Remnants of focal adhesion complexes dissociate from the cell cortex and coalesce into large structures that contain aggregated F-actin. Pervanadate, an inhibitor of protein- tyrosine phosphatases, abrogates all effects of cAMP. Conversely, genistein- sensitive protein-tyrosine kinase activity is essential for establishing epithelial morphology and reversing effects of cAMP in Y1 cells. Thus, cAMP/protein kinase A (PKA) actions are initially targeted to focal adhesions and cortical actin cytoskeleton; paxillin is an early and unexpected downstream target in a PKA-mediated signaling pathway, and protein-tyrosine phosphatase activity provides an essential link between PKA activation and the control of cell shape.
AB - Cyclic AMP induces corticosteroid production, differential gene transcription, and cell cycle arrest in adrenal cortex-derived Y1 cells. These responses follow a cAMP-controlled transformation in Y1 cell morphology: the conversion of flat epithelial cells into rounded, highly refractile cells with short processes. Little is known about effector proteins and mechanisms that link activated protein kinase A to the alteration in cell shape. We now report that cAMP causes rapid (≤1 min) and selective tyrosine dephosphorylation of paxillin, a focal adhesion protein. Paxillin is maximally dephosphorylated before other physiological effects of cAMP are detected in Y1 cells. Dephosphopaxillin translocates from focal adhesions to the cytoplasm as stress fibers vanish and F-actin accumulates in membrane ruffles and cytoplasmic aggregates. Remnants of focal adhesion complexes dissociate from the cell cortex and coalesce into large structures that contain aggregated F-actin. Pervanadate, an inhibitor of protein- tyrosine phosphatases, abrogates all effects of cAMP. Conversely, genistein- sensitive protein-tyrosine kinase activity is essential for establishing epithelial morphology and reversing effects of cAMP in Y1 cells. Thus, cAMP/protein kinase A (PKA) actions are initially targeted to focal adhesions and cortical actin cytoskeleton; paxillin is an early and unexpected downstream target in a PKA-mediated signaling pathway, and protein-tyrosine phosphatase activity provides an essential link between PKA activation and the control of cell shape.
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U2 - 10.1074/jbc.271.46.29211
DO - 10.1074/jbc.271.46.29211
M3 - Article
C2 - 8910579
AN - SCOPUS:0029842723
SN - 0021-9258
VL - 271
SP - 29211
EP - 29215
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 46
ER -