PMID- 10373465
OWN - NLM
STAT- MEDLINE
DCOM- 19990715
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 26
DP  - 1999 Jun 25
TI  - Phosphorylation at the cyclin-dependent kinases site (Thr85) of parathyroid
      hormone-related protein negatively regulates its nuclear localization.
PG  - 18559-66
AB  - Parathyroid hormone-related protein (PTHrP) is expressed by a wide variety of
      cells and is considered to act as a secreted factor; however, evidence is
      accumulating for it to act in an intracrine manner. We have determined that PTHrP
      localizes to the nucleus at the G1 phase of the cell cycle and is transported to 
      the cytoplasm when cells divide. PTHrP contains a putative nuclear localization
      sequence (NLS) (residues 61-94) similar to that of SV40 T-antigen, which may be
      implicated in the nuclear import of the molecule. We identified that Thr85
      immediately prior to the NLS of PTHrP was phosphorylated by CDC2-CDK2 and
      phosphorylation was cell cycle-dependent. Mutation of Thr85 to Ala85 resulted in 
      nuclear accumulation of PTHrP, while mutation to Glu85 to mimic a phosphorylated 
      residue resulted in localization of PTHrP to the cytoplasm. Combined, the data
      demonstrate that the intracellular localization of PTHrP is phosphorylation- and 
      cell cycle-dependent, and such control further supports a potential intracellular
      role (10,34,35) for PTHrP.
FAU - Lam, M H
AU  - Lam MH
AD  - St. Vincent's Institute of Medical Research and the Department of Medicine, The
      University of Melbourne, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia.
FAU - House, C M
AU  - House CM
FAU - Tiganis, T
AU  - Tiganis T
FAU - Mitchelhill, K I
AU  - Mitchelhill KI
FAU - Sarcevic, B
AU  - Sarcevic B
FAU - Cures, A
AU  - Cures A
FAU - Ramsay, R
AU  - Ramsay R
FAU - Kemp, B E
AU  - Kemp BE
FAU - Martin, T J
AU  - Martin TJ
FAU - Gillespie, M T
AU  - Gillespie MT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Neoplasm Proteins)
RN  - 0 (PTHLH protein, human)
RN  - 0 (Parathyroid Hormone)
RN  - 0 (Parathyroid Hormone-Related Protein)
RN  - 0 (Proteins)
RN  - 2ZD004190S (Threonine)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
SB  - IM
MH  - Biological Transport
MH  - Cell Line
MH  - Cell Nucleus/*metabolism
MH  - Cyclin-Dependent Kinases/*metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - Neoplasm Proteins/*metabolism
MH  - Parathyroid Hormone/*metabolism
MH  - Parathyroid Hormone-Related Protein
MH  - Phosphorylation
MH  - Proteins/*metabolism
MH  - S Phase
MH  - Spectrometry, Fluorescence
MH  - Threonine/*metabolism
EDAT- 1999/06/22 00:00
MHDA- 1999/06/22 00:01
CRDT- 1999/06/22 00:00
PHST- 1999/06/22 00:00 [pubmed]
PHST- 1999/06/22 00:01 [medline]
PHST- 1999/06/22 00:00 [entrez]
AID - 10.1074/jbc.274.26.18559 [doi]
AID - S0021-9258(19)87191-0 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Jun 25;274(26):18559-66. doi: 10.1074/jbc.274.26.18559.