PMID- 9255227
OWN - NLM
STAT- MEDLINE
DCOM- 19970904
LR  - 20190630
IS  - 0022-3476 (Print)
IS  - 0022-3476 (Linking)
VI  - 131
IP  - 1 Pt 2
DP  - 1997 Jul
TI  - Growth-hormone signal transduction.
PG  - S42-4
AB  - Growth hormone (GH) has long been recognized as one of the principal factors that 
      control postnatal growth. Advances made in the last 5 years have increased our 
      understanding of the intracellular signaling mechanisms subsequent to GH binding. 
      The earliest event in GH signaling appears to be the binding of a single GH 
      molecule by a pair of GH receptors (GHRs). The dimerization of GHRs leads to the 
      activation of Janus kinase 2 (JAK2), a nonreceptor tyrosine kinase that 
      associates with the cytoplasmic domain of GHR. It is thought that all signaling 
      downstream from GHR depends on this initial activation of JAK2. Once activated, 
      JAK2 tyrosyl-phosphorylates both itself and the cytoplasmic domain of GHR. These 
      phosphorylated tyrosine residues act as docking sites for various signaling 
      molecules that contain Src homology 2 (SH-2) or other phosphotyrosyl-binding 
      domains. The signaling molecules that are recruited and activated by the GHR-JAK2 
      complex include signal transducers and activators of transcription (Stat) 
      factors, the adapter protein Shc, and the insulin receptor substrates (IRSs) 1 
      and 2. The recruitment and activation of these signaling intermediates leads to 
      the activation of enzymes such as MAP kinase, phosphatidylinositol-3'-kinase, 
      protein kinase C, and phospholipase A2 and to the release of various second 
      messengers such as diacylglycerol, calcium, and nitric oxide. Ultimately, these 
      pathways modulate cellular functions such as gene transcription, metabolite 
      transport, and enzymatic activities that affect the GH-dependent control of 
      growth and metabolism.
FAU - Campbell, G S
AU  - Campbell GS
AD  - Department of Physiology, University of Michigan, Ann Arbor, USA.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - J Pediatr
JT  - The Journal of pediatrics
JID - 0375410
RN  - 0 (Diglycerides)
RN  - 0 (Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Somatotropin)
RN  - 0 (Transcription Factors)
RN  - 12629-01-5 (Human Growth Hormone)
RN  - 21820-51-9 (Phosphotyrosine)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, Insulin)
RN  - EC 2.7.10.2 (JAK2 protein, human)
RN  - EC 2.7.10.2 (Janus Kinase 2)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - EC 3.1.1.32 (Phospholipases A)
RN  - EC 3.1.1.4 (Phospholipases A2)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Calcium/metabolism
MH  - Child
MH  - Cytoplasm/metabolism
MH  - Diglycerides/metabolism
MH  - Dimerization
MH  - Enzyme Activation
MH  - Growth/physiology
MH  - Human Growth Hormone/*physiology
MH  - Humans
MH  - Janus Kinase 2
MH  - Mitogen-Activated Protein Kinase Kinases
MH  - Nitric Oxide/metabolism
MH  - Phosphatidylinositol 3-Kinases
MH  - Phospholipases A/metabolism
MH  - Phospholipases A2
MH  - Phosphorylation
MH  - Phosphotransferases (Alcohol Group Acceptor)/metabolism
MH  - Phosphotyrosine/metabolism
MH  - Protein Binding
MH  - Protein Kinase C/metabolism
MH  - Protein Kinases/metabolism
MH  - Protein-Tyrosine Kinases/physiology
MH  - Proteins/physiology
MH  - *Proto-Oncogene Proteins
MH  - Receptor, Insulin/physiology
MH  - Receptors, Somatotropin/physiology
MH  - Second Messenger Systems/physiology
MH  - Signal Transduction/*physiology
MH  - Transcription Factors/physiology
MH  - Transcription, Genetic
MH  - src Homology Domains/physiology
RF  - 22
EDAT- 1997/07/01 00:00
MHDA- 1997/07/01 00:01
CRDT- 1997/07/01 00:00
PHST- 1997/07/01 00:00 [pubmed]
PHST- 1997/07/01 00:01 [medline]
PHST- 1997/07/01 00:00 [entrez]
AID - a82770 [pii]
AID - 10.1016/s0022-3476(97)70010-6 [doi]
PST - ppublish
SO  - J Pediatr. 1997 Jul;131(1 Pt 2):S42-4. doi: 10.1016/s0022-3476(97)70010-6.