PMID- 10614620
OWN - NLM
STAT- MEDLINE
DCOM- 20000113
LR  - 20050813
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 141
IP  - 1
DP  - 2000 Jan
TI  - Dynamic regulation of RGS2 in bone: potential new insights into parathyroid
      hormone signaling mechanisms.
PG  - 28-36
AB  - The initial steps involved in mediating the transduction of PTH signal via its G 
      protein-coupled receptors are well understood and occur through the activation of
      cAMP and phospholipase C pathways. However, the cellular and molecular mechanisms
      for subsequent receptor desensitization are less well understood. Recently, a new
      family of GTPase activating proteins known as regulators of G protein signaling
      (RGS), has been implicated in desensitization of several G protein-coupled
      ligand-induced processes. At present, it is not known whether any of the RGS
      proteins play a role in PTH signaling. Using the differential display method, we 
      screened for genes that are selectively expressed after a single s.c. injection
      of human PTH (1-38) (8 microg/100 g) in osteoblast-enriched femoral metaphyseal
      spongiosa of young male rats (3-4 weeks old). We found and cloned one full-length
      complementary DNA that encodes a 211-amino acid RGS protein and shares 97%
      sequence identity with mouse and human RGS2. Based on sequence similarity, we
      have designated this clone as rat RGS2. Northern blot analysis confirmed that the
      expression of RGS2 messenger RNA (mRNA) is rapidly and transiently increased by
      human PTH (1-38) in both metaphyseal (4-to 5-fold) and diaphyseal (2- to 3-fold) 
      bone, as well as in cultured osteoblast cultures (2- to 37-fold). In vitro,
      forskolin and dibutyryl cAMP similarly elevated RGS2 mRNA. In vivo, PTH analog
      (1-31) [which stimulates intracellular cAMP accumulation, PTHrP (1-34), and
      prostaglandin E2] induced RGS2 mRNA expression; whereas PTH analogs (3-34) and
      (7-34), which do not stimulate cAMP production, had no effect on expression. In
      tissue distribution analysis, RGS2 is widely expressed and was detected in all
      tissues examined (heart, spleen, liver, skeletal muscle, kidney, and testis),
      with significant expression in two nonclassical PTH-sensitive tissues: the brain,
      and the heart. After PTH injection, RGS2 mRNA expression was induced in rat bone 
      but not in any of the other tissues examined. These findings demonstrate that
      RGS2 is regulated by PTH, prostaglandin E2, and PTHrP and that regulation by PTH 
      in bone occurs via the cAMP pathway. Additionally, these results suggest the
      exciting possibility that increased RGS2 expression in osteoblasts may be one of 
      the early events influencing PTH signaling.
FAU - Miles, R R
AU  - Miles RR
AD  - Endocrine Division, Lilly Research Labs, Indianapolis, Indiana 46285, USA.
FAU - Sluka, J P
AU  - Sluka JP
FAU - Santerre, R F
AU  - Santerre RF
FAU - Hale, L V
AU  - Hale LV
FAU - Bloem, L
AU  - Bloem L
FAU - Boguslawski, G
AU  - Boguslawski G
FAU - Thirunavukkarasu, K
AU  - Thirunavukkarasu K
FAU - Hock, J M
AU  - Hock JM
FAU - Onyia, J E
AU  - Onyia JE
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (DNA, Complementary)
RN  - 0 (Parathyroid Hormone)
RN  - 0 (RGS Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Rgs2 protein, mouse)
RN  - 24937-83-5 (Poly A)
SB  - AIM
SB  - IM
SB  - S
MH  - Amino Acid Sequence
MH  - Animals
MH  - Autocrine Communication/*physiology
MH  - Blotting, Northern
MH  - Bone and Bones/metabolism/*physiology
MH  - Cells, Cultured
MH  - DNA, Complementary/biosynthesis/genetics
MH  - Humans
MH  - Male
MH  - Mice
MH  - Molecular Sequence Data
MH  - Osteoblasts/metabolism
MH  - Parathyroid Hormone/*physiology
MH  - Poly A/isolation & purification
MH  - Polymerase Chain Reaction
MH  - RGS Proteins/*biosynthesis
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Up-Regulation
EDAT- 1999/12/30 00:00
MHDA- 1999/12/30 00:01
CRDT- 1999/12/30 00:00
PHST- 1999/12/30 00:00 [pubmed]
PHST- 1999/12/30 00:01 [medline]
PHST- 1999/12/30 00:00 [entrez]
AID - 10.1210/endo.141.1.7229 [doi]
PST - ppublish
SO  - Endocrinology. 2000 Jan;141(1):28-36. doi: 10.1210/endo.141.1.7229.