PMID- 10205165
OWN - NLM
STAT- MEDLINE
DCOM- 19990611
LR  - 20181113
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 18
IP  - 8
DP  - 1999 Apr 15
TI  - The p16(INK4a) tumour suppressor protein inhibits alphavbeta3 integrin-mediated
      cell spreading on vitronectin by blocking PKC-dependent localization of
      alphavbeta3 to focal contacts.
PG  - 2106-18
AB  - Expression of full-length p16(INK4a) blocks alphavbeta3 integrin-dependent cell
      spreading on vitronectin but not collagen IV. Similarly, G1-associated cell cycle
      kinases (CDK) inhibitory (CKI) synthetic peptides derived from p16(INK4a),
      p18(INK4c) and p21(Cip1/Waf1), which can be delivered directly into cells from
      the tissue culture medium, do not affect non-alphavbeta3-dependent spreading on
      collagen IV, laminin and fibronectin at concentrations that inhibit cell cycle
      progression in late G1. The alphavbeta3 heterodimer remains intact after CKI
      peptide treatment but is immediately dissociated from the focal adhesion
      contacts. Treatment with phorbol 12-myristate 13-acetate (PMA) allows alphavbeta3
      to locate to the focal adhesion contacts and the cells to spread on vitronectin
      in the presence of CKI peptides. The cdk6 protein is found to suppress
      p16(INK4a)-mediated inhibition of spreading and is also shown to localize to the 
      ruffling edge of spreading cells, indicating a function for cdk6 in controlling
      matrix-dependent cell spreading. These results demonstrate a novel G1
      CDK-associated integrin regulatory pathway that acts upstream of
      alphavbeta3-dependent activation of PKC as well as a novel function for the
      p16(INK4a) tumour suppressor protein in regulating matrix-dependent cell
      migration.
FAU - Fahraeus, R
AU  - Fahraeus R
AD  - CRC Laboratories, Department of Biochemistry, University of Dundee, Dundee DD1
      4HN, UK.
FAU - Lane, D P
AU  - Lane DP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Receptors, Vitronectin)
RN  - 0 (Vitronectin)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Amino Acid Sequence
MH  - Cell Adhesion/drug effects
MH  - Cell Line
MH  - Cell Movement/drug effects
MH  - Cyclin-Dependent Kinase Inhibitor p16/*metabolism
MH  - Cyclin-Dependent Kinases/antagonists & inhibitors
MH  - Dimerization
MH  - Enzyme Inhibitors/pharmacology
MH  - Humans
MH  - Molecular Sequence Data
MH  - Protein Kinase C/*antagonists & inhibitors
MH  - Receptors, Vitronectin/*metabolism
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Vitronectin/*metabolism
PMC - PMC1171295
EDAT- 1999/04/16 00:00
MHDA- 1999/04/16 00:01
CRDT- 1999/04/16 00:00
PHST- 1999/04/16 00:00 [pubmed]
PHST- 1999/04/16 00:01 [medline]
PHST- 1999/04/16 00:00 [entrez]
AID - 10.1093/emboj/18.8.2106 [doi]
PST - ppublish
SO  - EMBO J. 1999 Apr 15;18(8):2106-18. doi: 10.1093/emboj/18.8.2106.