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FLASH GENE
Symbol ROCK1 contributors: mct/pgu - updated : 21-05-2016
HGNC name Rho-associated, coiled-coil containing protein kinase 1
HGNC id 10251
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Hearing/Equilibriumearinnercochlea highly
Lymphoid/Immunelymph node   highly
Nervousnerve   highly
cells
SystemCellPubmedSpeciesStageRna symbol
Blood/Hematopoieticplatelet
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N terminal serine/threonine kinase domain
  • a long alpha-helix
  • a cysteine rich zing finger-like motif, phorbol-ester/DAG-type zinc finger
  • a REM (hr1) repeat
  • a central coiled-coil region containing a Rho binding site
  • a protein kinase domain
  • a C terminal pleckstrin homology domain (PH), and a RhoA-binding domain
  • auto-inhibitory domain interfering with kinase activity
  • HOMOLOGY
    Homologene
    FAMILY
  • protein kinase superfamily
  • AGC Ser/Thr protein kinase family
  • CATEGORY enzyme , regulatory , receptor nuclear membrane
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic
    basic FUNCTION
  • serine/threonine kinase that regulates cytokinesis, smooth muscle contraction, the formation of actin stress fibers and focal adhesions and the activation of the c-fos serum response element
  • required for centromere positioning and centromere- dependent exit from mitosis
  • phosphorylating the C-terminal residues Ser1131, Ser1137, and Thr1141 of FHOD1
  • plays an important role in the process of atherosclerosis
  • in bone marrow -derived cells mediates neointima formation following vascular injury
  • functions as a UVB sensor that regulates apoptosis, an important event in the prevention of skin cancer
  • key factor in regulation of motility/invasion of breast cancer cells
  • novel regulator of glucose homeostasis and insulin sensitivity, which could lead to new treatment approaches for obesity and type 2 diabetes
  • plays important roles in many cellular processes, including signal transduction, vesicle trafficking, and cytoskeletal organization
  • ROCK1 and ROCK2 play distinct roles in regulating keratinocyte adhesion and terminal differentiation
  • involved in controlling embryonic stem (ES) cell renewal and differentiation
  • promote embryonic stem cell colony formation, maintain them at undifferentiated state, and prevent them from neural differentiation at high seeding density, and its inhibition represents a new strategy for preparing large numbers of neural progenitor cells
  • participate in a variety of actin-based cellular processes including smooth muscle contraction, cell migration, and stress fiber formation
  • functional role in ameloblast differentiation
  • ROCK1 and JAK1 signaling cooperate to control actomyosin contractility in tumor cells and stroma
  • ROCK1/MARK2-dependent regulation of basement membrane placement is required for the coordination of tissue polarity and the elaboration of tissue structure in the developing submandibular salivary gland
  • ROCK1 and ROCK2 have distinct and separate roles in adhesion complex assembly and turnover in epidermal keratinocytes
  • ROCK1, ROCK2 are necessary for acquisition of elongated and geometric cell shape, two key events for epithelial differentiation
  • ROCK1 and ROCK2, negatively regulate CD1D-mediated Ag presentation
  • is involved in destabilizing actin cytoskeleton through regulating MLC2 phosphorylation and peripheral actomyosin contraction
  • ROCK1 and ROCK2, are involved in stress fiber assembly and cell adhesion and are assumed to be functionally redundant
  • is involved in destabilizing the actin cytoskeleton and cell detachment
  • role of the ROCK1 pathway during early stages of human neurogenesis
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
  • NOTCH1-ROCK1 pathway critical for cellular differentiation and loss of self-renewal capacity in a subset of immature cells
  • a component
  • FRMD6/PARD3-PRKCI-ROCK1 pathway that controls epithelial apical morphology
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • phosphorylating and activating LIMK1
  • downstream effector of RHO, phosphorylates and activates LIM kinase, which in turn, phosphorylates cofilin, inhibiting its actin-depolymerizing activity
  • direct cleavage substrate of activated caspase-3 (CASP3), which is associated with heart failure (in promoting apoptotic signals in myocardial hypertrophy and/or failure)
  • activity of ROCK1 was required for TAOK1 to induce cell contraction and membrane blebbing
  • RND3 binds to the N-terminal 420 AAs of ROCK1, which includes the kinase domain as well as N-terminal and C-terminal extensions
  • SHROOM3-ROCK1 interaction is crucial for the regulation of epithelial and neuroepithelial cell arrangement and remodeling
  • PFN1 interacts with HTT, as being a direct target of the ROCK1 isoform
  • MAPK8IP3 scaffolding protein is an interacting partner of ROCK1 (phosphorylation of MAPK8IP3 by ROCK1 was crucial for the recruitment of JNK)
  • KRIT1-CCM2 interaction regulates vascular barrier function by suppressing RHO/ROCK1 signaling and that this pathway is dysregulated in human CCM endothelium
  • physical interaction between CTNND1 and Rho-associated protein kinase 1 (ROCK1), a major effector of RHOA
  • MAPK8 activation is required for GNA12-induced invasion of breast cancer cells and MAPK8 is downstream of ROCK1 on this pathway
  • SHROOM2-ROCK1 interaction is sufficient to direct ROCK1 subcellular localization and the subsequent assembly of contractile actomyosin networks in defined subcellular locales
  • involvement of RHOA and ROCK1 in F11R relocalization
  • ROCK1 and ROCK2 could promote vascular smooth muscle cells (VSMC) proliferation through ERK nuclear translocation, regulating the expression of PCNA and cyclin D1 protein
  • cleavage of Rho associated Coiled Coil kinase I (ROCK 1) by CASP3 contributes to membrane blebbing
  • ROCK1 via LIMK1, LIMK2 regulates growth, maturation and actin based functions in mast cells
  • may promote cancer cell proliferation in prostate carcinoma by upregulating ROCK1
  • cell & other
    REGULATION
    activated by RHOA binding
    by caspase-3 cleavage plays an essential role in cardiac myocyte apoptosis
    inhibited by MYBPH, that inhibited ROCK1 and negatively regulated actomyosin organization, which in turn reduced single cell motility and increased collective cell migration, resulting in decreased cancer invasion and metastasis
    Phosphorylated by PRKCI, that phosphorylates ROCK1 and suppresses its junctional localization, thereby allowing cells to retain normally shaped apical domains
    Other ACTG1 regulates cell migration and modulates the ROCK1 signaling pathway
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    causes whole body insulin resistance by impairing insulin signaling in skeletal muscle, suggesting that activation of ROCK1 is essential for the normal actions of insulin on glucose transport in skeletal muscle
    tumoral somatic mutation     gain of function
    three somatic mutations leading to elevated kinase activity and driving actin cytoskeleton rearrangements that promote increased motility and decreased adhesion (characteristics of cancer progression)
    tumoral     --over  
    in various tumor cell lines and tumor tissues from osteosarcoma patients
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductivebreast
    potential target in breast cancer
    immunologyinflammatory 
    may represent a promising therapeutic target in vascular inflammatory diseases
    cancerbone 
    may be a promising therapeutic target for the treatment of osteosarcoma patients.
    neuromuscularspinal muscular atrophy 
    therapeutic potential of ROCK1 inhibition in SMA
    neurologyneurodegenerativehuntington chorea
    A signaling pathway from ROCK1 to profilin thus controls polyglutamine protein aggregation and is targeted by a promising therapeutic lead for HD
    ANIMAL & CELL MODELS
    ROCK1-deficient mice exhibited insulin resistance, as revealed by the failure of blood glucose levels to decrease after insulin injection