PMID- 10362354
OWN - NLM
STAT- MEDLINE
DCOM- 19990628
LR  - 20131121
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 22
DP  - 1999 Jun 3
TI  - Regulation and function of protein kinase B and MAP kinase activation by the
      IL-5/GM-CSF/IL-3 receptor.
PG  - 3334-42
AB  - Interleukin (IL)-3, IL-5 and granulocyte-macrophage colony-stimulating factor
      (GM-CSF) regulate proliferation, differentiation and apoptosis of target cells.
      Receptors for these cytokines consist of a cytokine-specific alpha subunit and a 
      common shared beta c subunit. Tyrosine phosphorylation of the beta c is thought
      to play a critical role in mediating signal transduction events. We have examined
      the effect of mutation of beta c tyrosines on the activation of multiple signal
      transduction pathways. Activation of protein kinase B (PKB) required JAK2 and was
      inhibited by dominant-negative phosphatidylinositol 3-kinase (P13K).
      Overexpression of JAK2 was sufficient to activate both protein kinase B (PKB) and
      extracellular regulated kinase-1 (ERK1). Tyrosine 577 and 612 were found to be
      critical for the activation of PKB and ERK1, but not activation of STAT
      transcription factors. Activation of both PKB and ERK have been implicated in the
      regulation of proliferation and apoptosis. We generated GM-CSFR stable cell lines
      expressing receptor mutants to evaluate their effect on these processes.
      Activation of both PKB and ERK was perturbed, while STAT activation remained
      unaffected. Tyrosines 577 and 612 were necessary for optimal proliferation,
      however, mutation of these tyrosine residues did not affect GM-CSF mediated
      rescue from apoptosis. These data demonstrate that while phosphorylation of beta 
      c tyrosine residues 577 and 612 are important for optimal cell proliferation,
      rescue from apoptosis can be mediated by alternative signalling routes apparently
      independent of PKB or ERK activation.
FAU - Dijkers, P F
AU  - Dijkers PF
AD  - Department of Pulmonary Diseases, University Hospital Utrecht, The Netherlands.
FAU - van Dijk, T B
AU  - van Dijk TB
FAU - de Groot, R P
AU  - de Groot RP
FAU - Raaijmakers, J A
AU  - Raaijmakers JA
FAU - Lammers, J W
AU  - Lammers JW
FAU - Koenderman, L
AU  - Koenderman L
FAU - Coffer, P J
AU  - Coffer PJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Interleukin-5)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Interleukin)
RN  - 0 (Receptors, Interleukin-3)
RN  - 0 (Receptors, Interleukin-5)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Transcription Factors)
RN  - 42HK56048U (Tyrosine)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Jak2 protein, mouse)
RN  - EC 2.7.10.2 (Janus Kinase 2)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Apoptosis/genetics
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Cell Division/drug effects/physiology
MH  - Cell Line/metabolism
MH  - Cell Survival
MH  - Enzyme Activation
MH  - Granulocyte-Macrophage Colony-Stimulating
      Factor/genetics/*metabolism/pharmacology
MH  - Interleukin-5/*metabolism
MH  - Janus Kinase 2
MH  - Mice
MH  - Mitogen-Activated Protein Kinase 3
MH  - *Mitogen-Activated Protein Kinases
MH  - Mutation
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation
MH  - *Protein-Serine-Threonine Kinases
MH  - Protein-Tyrosine Kinases/genetics/metabolism
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Receptors, Cell Surface/genetics/metabolism
MH  - Receptors, Interleukin/genetics/metabolism
MH  - Receptors, Interleukin-3/*metabolism
MH  - Receptors, Interleukin-5
MH  - Recombinant Proteins/genetics/metabolism
MH  - Signal Transduction
MH  - Transcription Factors/metabolism
MH  - Tyrosine/metabolism
EDAT- 1999/06/11 00:00
MHDA- 1999/06/11 00:01
CRDT- 1999/06/11 00:00
PHST- 1999/06/11 00:00 [pubmed]
PHST- 1999/06/11 00:01 [medline]
PHST- 1999/06/11 00:00 [entrez]
AID - 10.1038/sj.onc.1202678 [doi]
PST - ppublish
SO  - Oncogene. 1999 Jun 3;18(22):3334-42. doi: 10.1038/sj.onc.1202678.