PMID- 10087271
OWN - NLM
STAT- MEDLINE
DCOM- 19990614
LR  - 20190508
IS  - 0021-9525 (Print)
IS  - 0021-9525 (Linking)
VI  - 144
IP  - 6
DP  - 1999 Mar 22
TI  - Quantitative changes in integrin and focal adhesion signaling regulate myoblast
      cell cycle withdrawal.
PG  - 1295-309
AB  - We previously demonstrated contrasting roles for integrin alpha subunits and
      their cytoplasmic domains in controlling cell cycle withdrawal and the onset of
      terminal differentiation (Sastry, S., M. Lakonishok, D. Thomas, J. Muschler, and 
      A.F. Horwitz. 1996. J. Cell Biol. 133:169-184). Ectopic expression of the
      integrin alpha5 or alpha6A subunit in primary quail myoblasts either decreases or
      enhances the probability of cell cycle withdrawal, respectively. In this study,
      we addressed the mechanisms by which changes in integrin alpha subunit ratios
      regulate this decision. Ectopic expression of truncated alpha5 or alpha6A
      indicate that the alpha5 cytoplasmic domain is permissive for the proliferative
      pathway whereas the COOH-terminal 11 amino acids of alpha6A cytoplasmic domain
      inhibit proliferation and promote differentiation. The alpha5 and alpha6A
      cytoplasmic domains do not appear to initiate these signals directly, but instead
      regulate beta1 signaling. Ectopically expressed IL2R-alpha5 or IL2R-alpha6A have 
      no detectable effect on the myoblast phenotype. However, ectopic expression of
      the beta1A integrin subunit or IL2R-beta1A, autonomously inhibits differentiation
      and maintains a proliferative state. Perturbing alpha5 or alpha6A ratios also
      significantly affects activation of beta1 integrin signaling pathways. Ectopic
      alpha5 expression enhances expression and activation of paxillin as well as
      mitogen-activated protein (MAP) kinase with little effect on focal adhesion
      kinase (FAK). In contrast, ectopic alpha6A expression suppresses FAK and MAP
      kinase activation with a lesser effect on paxillin. Ectopic expression of
      wild-type and mutant forms of FAK, paxillin, and MAP/erk kinase (MEK) confirm
      these correlations. These data demonstrate that (a) proliferative signaling
      (i.e., inhibition of cell cycle withdrawal and the onset of terminal
      differentiation) occurs through the beta1A subunit and is modulated by the alpha 
      subunit cytoplasmic domains; (b) perturbing alpha subunit ratios alters paxillin 
      expression and phosphorylation and FAK and MAP kinase activation; (c)
      quantitative changes in the level of adhesive signaling through integrins and
      focal adhesion components regulate the decision of myoblasts to withdraw from the
      cell cycle, in part via MAP kinase.
FAU - Sastry, S K
AU  - Sastry SK
AD  - Department of Cell and Structural Biology, University of Illinois, Urbana,
      Illinois 61801, USA.
FAU - Lakonishok, M
AU  - Lakonishok M
FAU - Wu, S
AU  - Wu S
FAU - Truong, T Q
AU  - Truong TQ
FAU - Huttenlocher, A
AU  - Huttenlocher A
FAU - Turner, C E
AU  - Turner CE
FAU - Horwitz, A F
AU  - Horwitz AF
LA  - eng
GR  - R01 GM047607/GM/NIGMS NIH HHS/United States
GR  - R01 GM023244/GM/NIGMS NIH HHS/United States
GR  - GM47607/GM/NIGMS NIH HHS/United States
GR  - GM23244/GM/NIGMS NIH HHS/United States
GR  - R37 GM023244/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Antigens, CD)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Integrin alpha5)
RN  - 0 (Integrin alpha6)
RN  - 0 (Integrin beta1)
RN  - 0 (Integrins)
RN  - 0 (PXN protein, human)
RN  - 0 (Paxillin)
RN  - 0 (Phosphoproteins)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Focal Adhesion Kinase 1)
RN  - EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (PTK2 protein, human)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
SB  - IM
MH  - Animals
MH  - Antigens, CD/genetics/metabolism
MH  - Calcium-Calmodulin-Dependent Protein Kinases/metabolism
MH  - Cell Adhesion Molecules/*metabolism
MH  - Cell Cycle/*physiology
MH  - Cell Differentiation/physiology
MH  - Cell Division/physiology
MH  - Cells, Cultured
MH  - Coturnix
MH  - Cytoskeletal Proteins/metabolism
MH  - Focal Adhesion Kinase 1
MH  - Focal Adhesion Protein-Tyrosine Kinases
MH  - Humans
MH  - Integrin alpha5
MH  - Integrin alpha6
MH  - Integrin beta1/genetics/metabolism
MH  - Integrins/genetics/*metabolism
MH  - Muscle, Skeletal/*cytology/*metabolism
MH  - Paxillin
MH  - Phosphoproteins/metabolism
MH  - Protein-Tyrosine Kinases/*metabolism
MH  - Signal Transduction/*physiology
MH  - Transfection
PMC - PMC2150582
EDAT- 1999/03/24 00:00
MHDA- 1999/03/24 00:01
CRDT- 1999/03/24 00:00
PHST- 1999/03/24 00:00 [pubmed]
PHST- 1999/03/24 00:01 [medline]
PHST- 1999/03/24 00:00 [entrez]
AID - 10.1083/jcb.144.6.1295 [doi]
PST - ppublish
SO  - J Cell Biol. 1999 Mar 22;144(6):1295-309. doi: 10.1083/jcb.144.6.1295.