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integrin-linked protein kinase; 59 kD serine/threonine protein kinase; ILK-1; ILK-2; p59ILK (ILK, ILK1, ILK2)
Function:
- receptor-proximal protein kinase regulating integrin- mediated signal transduction
- may act as a mediator of inside-out integrin signaling
- focal adhesion protein part of the complex ILK-PINCH
- this complex is considered to be one of the convergence points of integrin- & growth factor-signaling pathway
- possible role in mediating cell architecture, adhesion to integrin substrates & anchorage-dependent growth in epithelial cells
- phosphorylates beta-1 & beta-3 integrin subunit on Ser & Thr,
- phosphorylates AKT1 & GSK3B
- stimulated rapidly but transiently by both cell fibronectin interactions, as well as by insulin (PI3-K-dependent), likely via the binding of Ptdins(3,4,5)P3 with a PH-like domain of ILK
- autophosphorylated on Ser
- interacts with cytoplasmic domain of integrin beta-1
- interacts with & is activated by LIMD2
- may also interact with integrin beta-2, integrin beta-3 &/or integrin beta-5
- interacts (via ANK repeats) with LIMS1 & LIMS2
- interacts with parvins & probably TGFB1I1
- interacts (via ANK repeats) with EPHA1 (via SAM domain);
- stimulated by EFNA1 but independent of the kinase activity of EPHA1
Structure:
- PH-like domain is involved in phosphatidylinositol phosphate binding
- belongs to the protein kinase superfamily, TKL Ser/Thr protein kinase family
- contains 5 ANK repeats
- contains 1 protein kinase domain
Compartment:
- cell junction, focal adhesion
- plasma membrane, cytoplasmic side
Expression:
- expressed in heart > skeletal muscle, pancreas & kidney > placenta, lung & liver
Pathology:
- may play a role in tumor metastasis [2]
General
ankyrin repeat domain protein (ANKRD)
serine/threonine kinase
Properties
SIZE: entity length = 452 aa
MW = 51 kD
COMPARTMENT: cytoplasm
MOTIF: ankyrin repeat
NAME: ankyrin repeat
SITE: 2-30
ankyrin repeat
NAME: ankyrin repeat
SITE: 31-63
LIMS1 interaction {33-139}
MOTIF: ankyrin repeat
NAME: ankyrin repeat
SITE: 64-96
ankyrin repeat
NAME: ankyrin repeat
SITE: 97-129
ankyrin repeat
NAME: ankyrin repeat
SITE: 130-174
PH-like; mediates interaction with TGFB1I1 {180-212}
MOTIF: Ser phosphorylation site {S186}
kinase domain
SITE: 193-446
MOTIF: ATP-binding site
NAME: ATP-binding site
SITE: 199-207
ATP-binding site
NAME: ATP-binding site
SITE: 220-220
STATE: active state
Database Correlations
OMIM 602366
UniProt Q13418
PFAM correlations
Entrez Gene 3611
Kegg hsa:3611
ENZYME 2.7.11.1
References
- UniProt :accession Q13418
- Peng H et al
LIMD2 Is a Small LIM-Only Protein Overexpressed in Metastatic
Lesions That Regulates Cell Motility and Tumor Progression by
Directly Binding to and Activating the Integrin-Linked Kinase.
Cancer Res March 1, 2014 74; 1390
PMID: 24590809
http://cancerres.aacrjournals.org/content/74/5/1390.abstract
Component-of
ILK-PINCH complex