Phosphorylation of AATYK1 by Cdk5 suppresses its tyrosine phosphorylation.
Apoptosis-associated tyrosine kinase 1 (AATYK1), a novel serine/threonine kinase that is highly expressed in the brain, is involved in neurite extension and apoptosis of cerebellar granule neurons; however, its precise function remains unknown. In this study, we investigated the interaction of AATYK1A with Cyclin-dependent kinase 5 (Cdk5)/p35, a proline-directed protein kinase that is predominantly expressed in neurons. AATYK1A bound to the p35 activation subunit of Cdk5 in cultured cells and in mouse brains and colocalized with p35 on endosomes in COS-7 cells. AATYK1A was phosphorylated at Ser34 by Cdk5/p35 in vitro, in cultured neurons and in mouse brain. In PC12D cells, Ser34 phosphorylation increased after treatment with nerve growth factor and phosphorylated AATYK1A accumulated in growth cones of PC12D cells. Ser34 phosphorylation suppressed the tyrosine phosphorylation of AATYK1A by Src family kinases. These results suggest a possibility that AATYK1A plays a role in early to recycling endosomes and its function is regulated by phosphorylation with Cdk5 or Src-family kinases.
Tsutsumi
Koji
K
Department of Biological Sciences, Tokyo Metropolitan University, Hachioji, Tokyo, Japan.
Takano
Tetsuya
T
Endo
Ryo
R
Fukuda
Mitsunori
M
Ohshima
Toshio
T
Tomomura
Mineko
M
Hisanaga
Shin-ichi
S
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism* / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D011992:Endosomes; D051379:Mice; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism* / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D014443:Tyrosine; C485554:Aatk protein, mouse; D011505:Protein-Tyrosine Kinases; D019061:src-Family Kinases; D051360:Cyclin-Dependent Kinase 5