Changes in motility, gene expression and actin dynamics: Cdk6-induced cytoskeletal changes associated with differentiation in mouse astrocytes.
Cyclin dependent kinase (cdk) 4 and cdk6 have historically been understood to be D-cyclin kinases that phosphorylate pRb in the nucleus to regulate G1 phase of the cell cycle. In conflict with this understood redundancy are several studies that have demonstrated a novel role for cdk6 in differentiation. Cdk6 expression must be reduced to allow proper osteoblast and osteoclast differentiation, enforced cdk6 expression blocked differentiation of mouse embryo fibroblasts, and cdk6 expression in primary astrocytes favored the expression of progenitor cell markers (Ericson et al. [2003] Mol Cancer Res 1:654-664; Matushansky et al. [2003] Oncogene 22:4143-4149; Ogasawara et al. [2004a] J Bone Miner Res 19:1128-1136; Ogasawara et al. [2004b] Mol Cell Biol 24:6560-6568). Experiments shown here investigate novel cytoplasmic and nuclear functions of cdk6. These data demonstrate that cdk6 expression in mouse astrocytes results in changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility. These changes in cdk6-infected cells are associated with the process of cellular differentiation.
Slomiany
Peter
P
Department of Biology, Connecticut College, New London, Connecticut, USA.
Baker
Thomas
T
Elliott
Emily R
ER
Grossel
Martha J
MJ
D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D001483:Base Sequence; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics* / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D004247:DNA / Q000235:genetics; D015870:Gene Expression; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D054461:Lim Kinases; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D054460:rho-Associated Kinases
D051339:Actin Depolymerizing Factors; D000199:Actins; D047908:Intracellular Signaling Peptides and Proteins; D004247:DNA; D011494:Protein Kinases; D054461:Lim Kinases; C515893:Limk1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; C495912:Cdk6 protein, mouse; D051361:Cyclin-Dependent Kinase 6