PTK2
Encyclopedia
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 and spreading processes. It has been shown that when FAK was blocked, breast cancer cells became less metastastic due to decreased mobility.
that is found concentrated in the focal adhesion
s that form among cells attaching to extracellular matrix
constituents. The encoded protein is a member of the FAK subfamily of protein tyrosine kinase
s that included PYK2 but lacks significant sequence similarity to kinases from other subfamilies. With the exception of certain types of blood cells, most cells express FAK. FAK tyrosine kinase
activity can be activated, which plays a key important early step in cell migration. FAK activity elicits intracellular signal transduction pathways that promote the turn-over of cell contacts with the extracellular matrix, promoting cell migration. FAK is required during development, with loss of FAK resulting in lethality. It seems to be a paradox that FAK is not absolutely required for cell migration, and may play other roles in the cell, including the regulation of the tumor suppressor p53
. At least four transcript variant
s encoding four different isoforms have been found for this gene, but the full-length natures of only two of them have been determined.
FAK is a protein of 125 kD recruited as a participant in focal adhesion dynamics between cells, and has a role in motility and cell survival. FAK is a highly conserved, non-receptor tyrosine kinase
originally identified as a substrate for the oncogene
protein tyrosine kinase v-src
. This cytosolic kinase has been implicated in diverse cellular roles including cell locomotion, mitogen response and cell survival. FAK is typically located at structures known as focal adhesion
s, these are multi-protein structures that link the extracellular matrix (ECM) to the cytoplasmic cytoskeleton
. Additional components of focal adhesions include actin
, filamin
, vinculin
, talin
, paxillin
and tensin
.
engagement, growth factor
stimulation, and the action of mitogenic neuropeptide
s. Integrin receptors are heterodimeric transmembrane glycoproteins that cluster upon ECM engagement leading to FAK phosphorylation and recruitment to focal adhesions.
(FAT), has been shown to be responsible for targeting FAK to focal adhesions. Paxillin
, a focal adhesion adaptor protein binds to FAK at a carboxy-terminal domain that overlaps the FAT domain.
The amino-terminal domains of FAK share a significant sequence similarity with the band 4.1 domain first identified in erythrocytes. This 4.1 band domain binds to the cytoplasmic region of transmembrane proteins including glycophorin C, actin and spectrin. This suggests that the amino-terminal region of FAK may have a role in anchoring the cytoskeleton, the exact nature of this role has not been clarified as yet.
with TSC2
, NCK1
, Janus kinase 2
, TLN1
, TGFB1I1
, BCAR1
, Deleted in Colorectal Cancer
, PIK3R1
, NEDD9
, Paxillin
, CRK
, Integrin, beta 5
, GIT1
, CD61
, STAT1
, PTEN
, Src
, BMX
, Grb2
, GRB7
, RB1CC1
, Syk
, FYN
, NEO1
, P53
, MAPK8IP3
, IRS1
and NCK2
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that, in humans, is encoded by the PTK2 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. PTK2 is a focal adhesion-associated protein kinase
Kinase
In chemistry and biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. Kinases are part of the larger family of phosphotransferases...
involved in cellular adhesion and spreading processes. It has been shown that when FAK was blocked, breast cancer cells became less metastastic due to decreased mobility.
Function
This gene encodes a cytosolic protein tyrosine kinaseTyrosine kinase
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a protein in a cell. It functions as an "on" or "off" switch in many cellular functions....
that is found concentrated in the focal adhesion
Focal adhesion
In cell biology, focal adhesions are specific types of large macromolecular assemblies through which both mechanical force and regulatory signals are transmitted. More precisely, they can be considered as sub-cellular macromolecules that mediate the regulatory effects In cell biology, focal...
s that form among cells attaching to extracellular matrix
Extracellular matrix
In biology, the extracellular matrix is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue in animals.Extracellular...
constituents. The encoded protein is a member of the FAK subfamily of protein tyrosine kinase
Tyrosine kinase
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a protein in a cell. It functions as an "on" or "off" switch in many cellular functions....
s that included PYK2 but lacks significant sequence similarity to kinases from other subfamilies. With the exception of certain types of blood cells, most cells express FAK. FAK tyrosine kinase
Tyrosine kinase
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a protein in a cell. It functions as an "on" or "off" switch in many cellular functions....
activity can be activated, which plays a key important early step in cell migration. FAK activity elicits intracellular signal transduction pathways that promote the turn-over of cell contacts with the extracellular matrix, promoting cell migration. FAK is required during development, with loss of FAK resulting in lethality. It seems to be a paradox that FAK is not absolutely required for cell migration, and may play other roles in the cell, including the regulation of the tumor suppressor p53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
. At least four transcript variant
Alternative splicing
Alternative splicing is a process by which the exons of the RNA produced by transcription of a gene are reconnected in multiple ways during RNA splicing...
s encoding four different isoforms have been found for this gene, but the full-length natures of only two of them have been determined.
FAK is a protein of 125 kD recruited as a participant in focal adhesion dynamics between cells, and has a role in motility and cell survival. FAK is a highly conserved, non-receptor tyrosine kinase
Tyrosine kinase
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a protein in a cell. It functions as an "on" or "off" switch in many cellular functions....
originally identified as a substrate for the oncogene
Oncogene
An oncogene is a gene that has the potential to cause cancer. In tumor cells, they are often mutated or expressed at high levels.An oncogene is a gene found in the chromosomes of tumor cells whose activation is associated with the initial and continuing conversion of normal cells into cancer...
protein tyrosine kinase v-src
Src (gene)
Proto-oncogene tyrosine-protein kinase Src is an enzyme that in humans is encoded by the SRC gene.Src is a proto-oncogene encoding a tyrosine kinase originally discovered by J. Michael Bishop and Harold E. Varmus, for which they won the 1989 Nobel Prize in Physiology or Medicine. It belongs to a...
. This cytosolic kinase has been implicated in diverse cellular roles including cell locomotion, mitogen response and cell survival. FAK is typically located at structures known as focal adhesion
Focal adhesion
In cell biology, focal adhesions are specific types of large macromolecular assemblies through which both mechanical force and regulatory signals are transmitted. More precisely, they can be considered as sub-cellular macromolecules that mediate the regulatory effects In cell biology, focal...
s, these are multi-protein structures that link the extracellular matrix (ECM) to the cytoplasmic cytoskeleton
Cytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...
. Additional components of focal adhesions include actin
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...
, filamin
FLNA
Filamin-A is a protein that in humans is encoded by the FLNA gene.- Function :Actin-binding protein, or filamin, is a 280-kD protein that crosslinks actin filaments into orthogonal networks in cortical cytoplasm and participates in the anchoring of membrane proteins for the actin cytoskeleton....
, vinculin
Vinculin
In mammalian cells, vinculin is a membrane-cytoskeletal protein in focal adhesion plaques that is involved in linkage of integrin adhesion molecules to the actin cytoskeleton...
, talin
Talin
Talin is a town in the Aragatsotn province of Armenia. It has a population of 5,371. The seventh century Talin Cathedral is located in the town.- History :...
, paxillin
Paxillin
Paxillin is a signal transduction adaptor protein discovered in 1990 in the laboratory of Keith Burridge and should not be confused with the neurotoxin paxilline. The C-terminal region of paxillin contains four LIM domains that target paxillin to focal adhesions, it is presumed through a direct...
and tensin
TNS1
Tensin-1 is a protein that in humans is encoded by the TNS1 gene.-External links:* Info with links in the -Further reading:...
.
Regulation
FAK is phosphorylated in response to integrinIntegrin
Integrins are receptors that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the ECM. They also play a role in cell signaling and thereby regulate cellular shape, motility, and the cell cycle....
engagement, growth factor
Growth factor
A growth factor is a naturally occurring substance capable of stimulating cellular growth, proliferation and cellular differentiation. Usually it is a protein or a steroid hormone. Growth factors are important for regulating a variety of cellular processes....
stimulation, and the action of mitogenic neuropeptide
Neuropeptide
Neuropeptides are small protein-like molecules used by neurons to communicate with each other. They are neuronal signaling molecules, influence the activity of the brain in specific ways and are thus involved in particular brain functions, like analgesia, reward, food intake, learning and...
s. Integrin receptors are heterodimeric transmembrane glycoproteins that cluster upon ECM engagement leading to FAK phosphorylation and recruitment to focal adhesions.
C-terminus
A carboxy-terminal region of one hundred and fifty-nine amino acids, the focal adhesion targeting domainFocal adhesion targeting region
In molecula biology, the focal adhesion targeting region is a conserved domain found on focal adhesion kinases.Focal adhesion kinases are tyrosine kinases found in focal adhesions, intracellular signalling complexes that are formed following engagement of the extracellular matrix by integrins...
(FAT), has been shown to be responsible for targeting FAK to focal adhesions. Paxillin
Paxillin
Paxillin is a signal transduction adaptor protein discovered in 1990 in the laboratory of Keith Burridge and should not be confused with the neurotoxin paxilline. The C-terminal region of paxillin contains four LIM domains that target paxillin to focal adhesions, it is presumed through a direct...
, a focal adhesion adaptor protein binds to FAK at a carboxy-terminal domain that overlaps the FAT domain.
N-terminus
The function of the amino-terminal domain is less clear, but it has been shown to interact with the beta-1 integrin subunit in vitro and is thought to be involved in the transduction of signals from ECM-integrin clusters. However, a recent study has called into question the importance of this interaction and suggested that interaction with the cytoplasmic region of the beta-3 integrin subunit is important.The amino-terminal domains of FAK share a significant sequence similarity with the band 4.1 domain first identified in erythrocytes. This 4.1 band domain binds to the cytoplasmic region of transmembrane proteins including glycophorin C, actin and spectrin. This suggests that the amino-terminal region of FAK may have a role in anchoring the cytoskeleton, the exact nature of this role has not been clarified as yet.
Catalytic/Regulatory Domain
Between the amino and the carboxy regions lies the catalytic domain. Phosphorylation of the activation loop within this kinase domain is important for the kinase activity of FAK.Interactions
PTK2 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with TSC2
TSC2
Tuberous sclerosis protein 2, also known as TSC2 and Tuberin, is a human protein and gene.-Interactions:TSC2 has been shown to interact with FOXO1, GSK3B, Peptidylglycine alpha-amidating monooxygenase, RAP1A, MAPK1, AKT1, AXIN1, TSC1, PTK2, Protein kinase, AMP-activated, alpha 1, YWHAZ, RPS6KA1,...
, NCK1
NCK1
Cytoplasmic protein NCK1 is a protein that in humans is encoded by the NCK1 gene.-Interactions:NCK1 has been shown to interact with DNM1, EIF2B2, KHDRBS1, Lymphocyte cytosolic protein 2, EPH receptor B1, SOCS7, MINK1, MAP4K1, MAP4K4, Abl gene, WIPF1, RRAS, Wiskott-Aldrich syndrome protein,...
, Janus kinase 2
Janus kinase 2
Janus kinase 2 is a human protein that has been implicated in signaling by members of the type II cytokine receptor family , the GM-CSF receptor family , the gp130 receptor family , and the single chain receptors...
, TLN1
TLN1
Talin-1 is a protein that in humans is encoded by the TLN1 gene.-Interactions:TLN1 has been shown to interact with PTK2, Paxillin and CD61.-Further reading:...
, TGFB1I1
TGFB1I1
Transforming growth factor beta-1-induced transcript 1 protein is a protein that in humans is encoded by the TGFB1I1 gene.-Interactions:TGFB1I1 has been shown to interact with PTPN12, PTK2, Androgen receptor, PTK2B, Dopamine transporter and Hsp27....
, BCAR1
BCAR1
Breast cancer anti-estrogen resistance protein 1 is a protein that in humans is encoded by the BCAR1 gene.-External links:* Info with links in the...
, Deleted in Colorectal Cancer
Deleted in Colorectal Cancer
Deleted in Colorectal Carcinoma, also known as DCC, is a protein which in humans is encoded by the DCC gene. DCC has long been implicated in colorectal cancer. While the official, full name of this gene is Deleted in Colorectal Carcinoma, it is almost universally called Deleted in Colorectal Cancer...
, PIK3R1
PIK3R1
Phosphatidylinositol 3-kinase regulatory subunit alpha is an enzyme that in humans is encoded by the PIK3R1 gene.-Interactions:PIK3R1 has been shown to interact with EPH receptor A2, KHDRBS1, Lymphocyte cytosolic protein 2, Janus kinase 2, GAB2, CD117, BCAR1, CD28, SHB, EZR, PIK3CD, GAB1, HRAS,...
, NEDD9
NEDD9
Enhancer of filamentation 1 is a protein that in humans is encoded by the NEDD9 gene.-Interactions:NEDD9 has been shown to interact with ID2, LYN, NCK1, MICAL1, CDH1, Abl gene, PTK2, CRKL, CRK and Mothers against decapentaplegic homolog 3....
, Paxillin
Paxillin
Paxillin is a signal transduction adaptor protein discovered in 1990 in the laboratory of Keith Burridge and should not be confused with the neurotoxin paxilline. The C-terminal region of paxillin contains four LIM domains that target paxillin to focal adhesions, it is presumed through a direct...
, CRK
CRK (gene)
Adapter molecule crk also known as proto-oncogene c-Crk or p38 is a protein that in humans is encoded by the CRK gene.- Function :...
, Integrin, beta 5
Integrin, beta 5
Integrin beta-5 is a protein that in humans is encoded by the ITGB5 gene.-Interactions:Integrin, beta 5 has been shown to interact with PTK2, Annexin A5 and PAK4.-External links:* Info with links in the...
, GIT1
GIT1
ARF GTPase-activating protein GIT1 is an enzyme that in humans is encoded by the GIT1 gene.GIT1 contains an ARFGAP domain, Anykrin repeats, and a GRK-interacting domain. The Arf-GAP domain, which enables it to act as a GTPase activating protein for the Arf family of GTPases, has been shown to be...
, CD61
CD61
Integrin beta-3 or CD61 is a protein that in humans is encoded by the ITGB3 gene. CD61 is a cluster of differentiation found on thrombocytes.-Structure and function:...
, STAT1
STAT1
STAT1 is a member of the Signal Transducers and Activators of Transcription family of transcription factors. STAT1 is involved in upregulating genes due to a signal by either type I, type II or type III interferons...
, PTEN
PTEN (gene)
Phosphatase and tensin homolog is a protein that, in humans, is encoded by the PTEN gene. Mutations of this gene are a step in the development of many cancers....
, Src
Src (gene)
Proto-oncogene tyrosine-protein kinase Src is an enzyme that in humans is encoded by the SRC gene.Src is a proto-oncogene encoding a tyrosine kinase originally discovered by J. Michael Bishop and Harold E. Varmus, for which they won the 1989 Nobel Prize in Physiology or Medicine. It belongs to a...
, BMX
BMX (gene)
Cytoplasmic tyrosine-protein kinase BMX is an enzyme that in humans is encoded by the BMX gene.-Interactions:BMX has been shown to interact with PAK1, PTK2, PTPN21 and RUFY1.-Further reading:...
, Grb2
Grb2
Growth factor receptor-bound protein 2 also known as Grb2 is an adaptor protein involved in signal transduction/cell communication. In humans, the GRB2 protein is encoded by the GRB2 gene....
, GRB7
GRB7
Growth factor receptor-bound protein 7, also known as GRB7, is a protein which in humans is encoded by the GRB7 gene.- Function :The product of this gene belongs to a small family of adaptor proteins that are known to interact with a number of receptor tyrosine kinases and signaling molecules...
, RB1CC1
RB1CC1
RB1-inducible coiled-coil protein 1 is a protein that in humans is encoded by the RB1CC1 gene.-Interactions:RB1CC1 has been shown to interact with PTK2B, ASK1 and PTK2.-Further reading:...
, Syk
Syk
Spleen tyrosine kinase, also known as Syk, is an enyzme which in humans is encoded by the SYK gene.- Function :SYK, along with Zap-70, is a member of the Syk family of tyrosine kinases...
, FYN
FYN
Proto-oncogene tyrosine-protein kinase Fyn is an enzyme that in humans is encoded by the FYN gene.This gene is a member of the protein-tyrosine kinase oncogene family. It encodes a membrane-associated tyrosine kinase that has been implicated in the control of cell growth...
, NEO1
NEO1
Neogenin is a protein that in humans is encoded by the NEO1 gene.-Further reading:...
, P53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
, MAPK8IP3
MAPK8IP3
C-jun-amino-terminal kinase-interacting protein 3 is an enzyme that in humans is encoded by the MAPK8IP3 gene.-Interactions:MAPK8IP3 has been shown to interact with ASK1, C-Raf, PTK2, MAPK10, Mitogen-activated protein kinase 9, MAPK8, MAP2K1, KLC2, MAP2K7, KLC1, MAPK8IP2 and MAP2K4.-Further reading:...
, IRS1
IRS1
Insulin receptor substrate 1 is a protein that in humans is encoded by the IRS-1 gene.-Function:Insulin receptor substrate 1 plays a key role in transmitting signals from the insulin and insulin-like growth factor-1 receptors to intracellular pathways PI3K / Akt and Erk MAP kinase...
and NCK2
NCK2
Cytoplasmic protein NCK2 is a protein that in humans is encoded by the NCK2 gene.-Interactions:NCK2 has been shown to interact with LIMS1, Epidermal growth factor receptor, PDGFRB, PTK2, T-cell surface glycoprotein CD3 epsilon chain and TrkB....
.
External links
- FAK Info with links in the Cell Migration Gateway