Adapter molecule crk also known as proto-oncogene c-Crk is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the ''CRK''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
The CRK protein participates in the
Reelin
Reelin, encoded by the ''RELN'' gene, is a large secreted extracellular matrix glycoprotein that helps regulate processes of neuronal migration and positioning in the developing brain by controlling cell–cell interactions. Besides this import ...
signaling cascade downstream of
DAB1
The Disabled-1 (Dab1) gene encodes a key regulator of Reelin signaling. Reelin is a large glycoprotein secreted by neurons of the developing brain, particularly Cajal-Retzius cells. DAB1 functions downstream of Reln in a signaling pathway
that c ...
.
Function
Adapter molecule crk is a member of an
adapter protein family that binds to several tyrosine-phosphorylated proteins. This protein has several
SH2 and
SH3 domains (src-homology domains) and is involved in several signaling pathways, recruiting cytoplasmic proteins in the vicinity of
tyrosine kinase
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions.
Tyrosine kinases belong to a larger cla ...
through SH2-phosphotyrosine interaction. The
N-terminal
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...
SH2 domain of this protein functions as a positive regulator of transformation whereas the
C-terminal
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
SH3 domain functions as a negative regulator of transformation. Two alternative transcripts encoding different isoforms with distinct biological activity have been described.
Crk together with
CrkL
Crk-like protein is a protein that in humans is encoded by the CRKL gene.
Function
v-CRK avian sarcoma virus CT10-homolog-like contains one SH2 domain and two SH3 domains. CRKL has been shown to activate the RAS and JUN kinase signaling pathw ...
participates in the
Reelin
Reelin, encoded by the ''RELN'' gene, is a large secreted extracellular matrix glycoprotein that helps regulate processes of neuronal migration and positioning in the developing brain by controlling cell–cell interactions. Besides this import ...
signaling cascade downstream of
DAB1
The Disabled-1 (Dab1) gene encodes a key regulator of Reelin signaling. Reelin is a large glycoprotein secreted by neurons of the developing brain, particularly Cajal-Retzius cells. DAB1 functions downstream of Reln in a signaling pathway
that c ...
.
v-Crk, a transforming oncoprotein from avian sarcoma viruses, is a fusion of viral "gag" protein with the SH2 and SH3 domains of cellular Crk.
The name Crk is from "CT10 Regulator of Kinase" where CT10 is the avian virus from which was isolated a protein, lacking kinase domains, but capable of stimulating phosphorylation of tyrosines in cells.
Crk should not be confused with
Src, which also has cellular (c-Src) and viral (v-Src) forms and is involved in some of the same signaling pathways but is a protein tyrosine-kinase.
Interactions
CRK (gene) has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with:
*
BCAR1
Breast cancer anti-estrogen resistance protein 1 is a protein that in humans is encoded by the ''BCAR1'' gene.
Gene
BCAR1 is localized on chromosome 16 on region q, on the negative strand and it consists of seven exons. Eight different gene is ...
,
*
Cbl gene
''Cbl'' (named after Casitas B-lineage Lymphoma) is a mammalian gene encoding the protein CBL which is an E3 ubiquitin-protein ligase involved in cell signalling and protein ubiquitination. Mutations to this gene have been implicated in a numb ...
,
*
Dock180
Dock180, (Dedicator of cytokinesis) also known as DOCK1, is a large (~180 kDa) protein involved in intracellular signalling networks. It is the mammalian ortholog of the ''C. elegans'' protein CED-5 and belongs to the DOCK family of Guanine nucl ...
,
* EPS15
Epidermal growth factor receptor substrate 15 is a protein that in humans is encoded by the ''EPS15'' gene.
Function
This gene encodes a protein that is part of the EGFR pathway. The protein is present at clathrin-coated pits and is involved i ...
,
* Epidermal growth factor receptor
The epidermal growth factor receptor (EGFR; ErbB-1; HER1 in humans) is a transmembrane protein that is a receptor for members of the epidermal growth factor family (EGF family) of extracellular protein ligands.
The epidermal growth factor recept ...
,[9614078 ]
* Grb2,
* IRS4
Insulin receptor substrate 4 is a protein that in humans is encoded by the ''IRS4'' gene.
IRS4 encodes the insulin receptor substrate 4, a cytoplasmic protein that contains many potential tyrosine and serine/threonine phosphorylation sites. Tyros ...
,
* MAP4K1
Mitogen-activated protein kinase kinase kinase kinase 1 is a protein kinase that in humans is encoded by the ''MAP4K1'' gene. It is also known as HPK1 (Hematopoietic Progenitor Kinase 1). The protein has been shown to play a role in JNK activatio ...
,
* MAPK8,
* NEDD9
Neural precursor cell expressed developmentally down-regulated protein 9 (NEDD-9) is a protein that in humans is encoded by the ''NEDD9'' gene. NEDD-9 is also known as enhancer of filamentation 1 (EF1), CRK-associated substrate-related protein (CA ...
,
* PDGFRA PDGFRA, i.e. platelet-derived growth factor receptor A, also termed PDGFRα, i.e. platelet-derived growth factor receptor α, or CD140a i.e. Cluster of Differentiation 140a, is a receptor located on the surface of a wide range of cell types. This re ...
,
* PDGFRB
Platelet-derived growth factor receptor beta is a protein that in humans is encoded by the ''PDGFRB'' gene. Mutations in PDGFRB are mainly associated with the clonal eosinophilia class of malignancies.
Gene
The ''PDGFRB'' gene is located on hu ...
,
* PTK2
PTK2 protein tyrosine kinase 2 (PTK2), also known as focal adhesion kinase (FAK), is a protein that, in humans, is encoded by the ''PTK2'' gene. PTK2 is a focal adhesion-associated protein kinase involved in cellular adhesion (how cells stick to ...
,[
* ]Paxillin
Paxillin is a protein that in humans is encoded by the ''PXN'' gene. Paxillin is expressed at focal adhesions of non-striated cells and at costameres of striated muscle cells, and it functions to adhere cells to the extracellular matrix. Mutation ...
* RAPGEF1
Rap guanine nucleotide exchange factor 1 is a protein that in humans is encoded by the ''RAPGEF1'' gene.
Function
The protein encoded by this gene is a human guanine nucleotide releasing protein for Ras protein. It belongs to the adaptor-type S ...
,
* RICS
The Royal Institution of Chartered Surveyors (RICS) is a global professional body for surveyors, founded in London in 1868. It works at a cross-governmental level, and aims to promote and enforce the highest international standards in the val ...
,
* SH3KBP1
SH3 domain-containing kinase-binding protein 1 (synonyms - CIN85, in rodents - Ruk) is an adaptor protein that in humans is encoded by the ''SH3KBP1'' gene.
Function
CBL (MIM 165360) constitutively interacts with SH3 domain-containing protein ...
, and
* SOS1
Son of sevenless homolog 1 is a protein that in humans is encoded by the ''SOS1'' gene.
Function
SOS1 is a guanine nucleotide exchange factor (GEF) which interacts with RAS proteins to phosphorylate GDP into GTP, or from an inactive state to an ...
.[
]
See also
*CrkL
Crk-like protein is a protein that in humans is encoded by the CRKL gene.
Function
v-CRK avian sarcoma virus CT10-homolog-like contains one SH2 domain and two SH3 domains. CRKL has been shown to activate the RAS and JUN kinase signaling pathw ...
, "Crk-like" protein
References
Further reading
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External links
Crk
Info with links in th
Cell Migration Gateway
*
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* {{UCSC gene info, CRK
Genes
Human proteins