PMID- 10526130
OWN - NLM
STAT- MEDLINE
DCOM- 19991221
LR  - 20190614
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 842
IP  - 2
DP  - 1999 Sep 25
TI  - pRb phosphorylation is regulated differentially by cyclin-dependent kinase (Cdk) 
      2 and Cdk4 in retinoic acid-induced neuronal differentiation of P19 cells.
PG  - 342-50
AB  - The retinoblastoma protein (pRb) is a key regulator of cell growth,
      differentiation and survival. pRb(-/-) mice show abnormal neuronal cell death in 
      the developing brain. The function of pRb is regulated by its phosphorylation
      state. In this study, the phosphorylation of pRb during retinoic acid
      (RA)-induced neuronal differentiation of P19 cells was examined using
      site-specific antibodies against pRb phosphorylated at Ser601, Ser605 and Ser773.
      Although pRb was hyperphosphorylated in undifferentiated P19 cells, Ser601 and
      Ser773 were not phosphorylated. Upon exposure to RA, however, these two sites
      became strongly phosphorylated. Cdk4 kinase activity was almost undetectable in
      undifferentiated P19 cells, but was strongly activated on exposure to RA. In
      contrast, Cdk2 kinase activity and the phosphorylation of Ser605 were observed in
      undifferentiated cells as well as in RA-treated cells. These observations suggest
      that Cdk2 and Cdk4 may phosphorylate different sites of pRb in vivo and that the 
      two sites of pRb examined here are newly phosphorylated during RA-induced
      neuronal differentiation in P19 cells.
FAU - Watanabe, Y
AU  - Watanabe Y
AD  - Department of Molecular Immunology, Medical Institute of Bioregulation, Kyushu
      University, Maidashi 3-1-1, Higashi-ku, Fukuoka, Japan.
FAU - Watanabe, T
AU  - Watanabe T
FAU - Kitagawa, M
AU  - Kitagawa M
FAU - Taya, Y
AU  - Taya Y
FAU - Nakayama, K
AU  - Nakayama K
FAU - Motoyama, N
AU  - Motoyama N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Retinoblastoma Protein)
RN  - 17885-08-4 (Phosphoserine)
RN  - 452VLY9402 (Serine)
RN  - 5688UTC01R (Tretinoin)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.22 (CDC2-CDC28 Kinases)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 2)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - *CDC2-CDC28 Kinases
MH  - Cell Cycle
MH  - Cell Differentiation/drug effects
MH  - Cell Line
MH  - Cyclin-Dependent Kinase 2
MH  - Cyclin-Dependent Kinase 4
MH  - Cyclin-Dependent Kinases/*metabolism
MH  - Kinetics
MH  - Neurons/cytology/drug effects/*metabolism
MH  - Phosphorylation
MH  - Phosphoserine/metabolism
MH  - Protein-Serine-Threonine Kinases/*metabolism
MH  - *Proto-Oncogene Proteins
MH  - Retinoblastoma Protein/*metabolism
MH  - Serine
MH  - Tretinoin/*pharmacology
EDAT- 1999/10/20 00:00
MHDA- 1999/10/20 00:01
CRDT- 1999/10/20 00:00
PHST- 1999/10/20 00:00 [pubmed]
PHST- 1999/10/20 00:01 [medline]
PHST- 1999/10/20 00:00 [entrez]
AID - S0006899399018442 [pii]
AID - 10.1016/s0006-8993(99)01844-2 [doi]
PST - ppublish
SO  - Brain Res. 1999 Sep 25;842(2):342-50. doi: 10.1016/s0006-8993(99)01844-2.