PMID- 10022929
OWN - NLM
STAT- MEDLINE
DCOM- 19990325
LR  - 20190508
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 19
IP  - 3
DP  - 1999 Mar
TI  - The LIM-only protein PINCH directly interacts with integrin-linked kinase and is 
      recruited to integrin-rich sites in spreading cells.
PG  - 2425-34
AB  - PINCH is a widely expressed and evolutionarily conserved protein comprising
      primarily five LIM domains, which are cysteine-rich consensus sequences
      implicated in mediating protein-protein interactions. We report here that PINCH
      is a binding protein for integrin-linked kinase (ILK), an intracellular
      serine/threonine protein kinase that plays important roles in the cell adhesion, 
      growth factor, and Wnt signaling pathways. The interaction between ILK and PINCH 
      has been consistently observed under a variety of experimental conditions. They
      have interacted in yeast two-hybrid assays, in solution, and in solid-phase-based
      binding assays. Furthermore, ILK, but not vinculin or focal adhesion kinase, has 
      been coisolated with PINCH from mammalian cells by immunoaffinity chromatography,
      indicating that PINCH and ILK associate with each other in vivo. The PINCH-ILK
      interaction is mediated by the N-terminal-most LIM domain (LIM1, residues 1 to
      70) of PINCH and multiple ankyrin (ANK) repeats located within the N-terminal
      domain (residues 1 to 163) of ILK. Additionally, biochemical studies indicate
      that ILK, through the interaction with PINCH, is capable of forming a ternary
      complex with Nck-2, an SH2/SH3-containing adapter protein implicated in growth
      factor receptor kinase and small GTPase signaling pathways. Finally, we have
      found that PINCH is concentrated in peripheral ruffles of cells spreading on
      fibronectin and have detected clusters of PINCH that are colocalized with the
      alpha5beta1 integrins. These results demonstrate a specific protein recognition
      mechanism utilizing a specific LIM domain and multiple ANK repeats and suggest
      that PINCH functions as an adapter protein connecting ILK and the integrins with 
      components of growth factor receptor kinase and small GTPase signaling pathways.
FAU - Tu, Y
AU  - Tu Y
AD  - Department of Cell Biology and The Cell Adhesion and Matrix Research Center,
      University of Alabama at Birmingham, Birmingham, Alabama 35294-0019, USA.
FAU - Li, F
AU  - Li F
FAU - Goicoechea, S
AU  - Goicoechea S
FAU - Wu, C
AU  - Wu C
LA  - eng
GR  - R01 DK054639/DK/NIDDK NIH HHS/United States
GR  - DK54639/DK/NIDDK 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  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Ankyrins)
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Fibronectins)
RN  - 0 (Integrins)
RN  - 0 (LIM Domain Proteins)
RN  - 0 (LIMS1 protein, human)
RN  - 0 (Membrane Proteins)
RN  - 0 (Receptors, Vitronectin)
RN  - 0 (integrin alphavbeta1)
RN  - EC 2.7.1.- (integrin-linked kinase)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Ankyrins/genetics
MH  - Binding Sites
MH  - Carrier Proteins/genetics/metabolism
MH  - Cell Adhesion
MH  - Cell Line
MH  - Cell Movement
MH  - Chromosome Mapping
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Fibronectins/metabolism
MH  - Humans
MH  - Integrins/*metabolism
MH  - LIM Domain Proteins
MH  - Membrane Proteins
MH  - Nucleic Acid Hybridization
MH  - Protein-Serine-Threonine Kinases/genetics/*metabolism
MH  - Rats
MH  - *Receptors, Vitronectin
MH  - Signal Transduction
MH  - Yeasts
PMC - PMC84035
EDAT- 1999/02/18 00:00
MHDA- 1999/02/18 00:01
CRDT- 1999/02/18 00:00
PHST- 1999/02/18 00:00 [pubmed]
PHST- 1999/02/18 00:01 [medline]
PHST- 1999/02/18 00:00 [entrez]
AID - 10.1128/mcb.19.3.2425 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1999 Mar;19(3):2425-34. doi: 10.1128/mcb.19.3.2425.