CRKL
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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 pathways and transform fibroblasts in a RAS-dependent fashion. It is a substrate of the BCR-ABL tyrosine kinase and plays a role in fibroblast transformation by BCR-ABL. In addition, CRKL has oncogenic potential. CrkL together with Crk participates in the Reelin signaling cascade downstream of DAB1. Interactions CRKL has been shown to interact with: * Abl gene, * BCAR1, * BCR gene, * CBLB, * CD117, * CD34, * Cbl gene, * Dock2, * EPOR, * GAB1, * GAB2, * INPP5D, * MAP4K1, * MAP4K5, * NEDD9, * PIK3R2, * Paxillin * RAPGEF1, * RICS, * STAT5A, * Syk, and * WAS Was or WAS may refer to: * ''Was'', a past-tense form of the English copular verb ''to be'' People * David Was (born c. 1952), the stage name of multi-instrume ...
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PIK3R2
Phosphatidylinositol 3-kinase regulatory subunit beta is an enzyme that in humans is encoded by the ''PIK3R2'' gene. A recent study on gene expression indicated that the PIK3R2 gene might have a key role in pan-cancer prognosis. Interactions PIK3R2 has been shown to interact with: * CRKL * Cbl gene, * Epidermal growth factor, * FYN, * HER2/neu, * Macrophage colony-stimulating factor, and * PIK3CD. Clinical relevance PIK3R2 mutations were recently shown to be associated with polymicrogyria Polymicrogyria (PMG) is a condition that affects the development of the human brain by multiple small gyri ( microgyri) creating excessive folding of the brain leading to an abnormally thick cortex. This abnormality can affect either one region o .... References Further reading

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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 number of human cancers, particularly acute myeloid leukaemia. Discovery In 1989 a virally encoded portion of the chromosomal mouse ''Cbl'' gene was the first member of the Cbl family to be discovered and was named ''v-Cbl'' to distinguish it from normal mouse ''c-Cbl''. The virus used in the experiment was a mouse-tropic strain of Murine leukemia virus isolated from the brain of a mouse captured at Lake Casitas, California known as ''Cas-Br-M'', and was found to have excised approximately a third of the original ''c-Cbl'' gene from a mouse into which it was injected. Sequencing revealed that the portion carried by the retrovirus encoded a ''tyrosine kinase binding domain'', and that this was the oncogenic form as retroviruses carrying ful ...
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CD117
Proto-oncogene c-KIT is the gene encoding the receptor tyrosine kinase protein known as tyrosine-protein kinase KIT, CD117 (cluster of differentiation 117) or mast/stem cell growth factor receptor (SCFR). Multiple transcript variants encoding different isoforms have been found for this gene. KIT was first described by the German biochemist Axel Ullrich in 1987 as the cellular homolog of the feline sarcoma viral oncogene v-kit. Function KIT is a cytokine receptor expressed on the surface of hematopoietic stem cells as well as other cell types. Altered forms of this receptor may be associated with some types of cancer. KIT is a receptor tyrosine kinase type III, which binds to stem cell factor , also known as "steel factor" or "c-kit ligand". When this receptor binds to stem cell factor (SCF) it forms a dimer that activates its intrinsic tyrosine kinase activity, that in turn phosphorylates and activates signal transduction molecules that propagate the signal in the cell. After ...
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MAP4K5
Mitogen-activated protein kinase kinase kinase kinase 5 is an enzyme that in humans is encoded by the ''MAP4K5'' gene. This gene encodes a member of the serine/threonine protein kinase family, that is highly similar to yeast SPS1/STE20 kinase. Yeast SPS1/STE20 functions near the beginning of the MAP kinase signal cascades that is essential for yeast pheromone response. This kinase was shown to activate Jun kinase in mammalian cells, which suggested a role in stress response. Two alternatively spliced transcript variants encoding the same protein have been described for this gene. Interactions MAP4K5 has been shown to interact with CRKL and TRAF2 TNF receptor-associated factor 2 is a protein that in humans is encoded by the ''TRAF2'' gene. Function The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, an .... References Further reading

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GAB1
GRB2-associated-binding protein 1 is a protein that in humans is encoded by the ''GAB1'' gene. Function The protein encoded by this gene is a member of the IRS1-like multisubstrate docking protein family. The encoded protein is an important mediator of branching tubulogenesis and plays a central role in cellular growth response, transformation and apoptosis. Two transcript variants encoding different isoforms have been found for this gene. GAB1 is involved also in the tonic pAKT activity in malignant B cells, and induces PI3K activation irrespectively of BCR stimulation by antigen. Interactions GAB1 has been shown to Protein-protein interaction, interact with: * CRKL, * Grb2, * MAP3K3, * PIK3R1, * PLCG1 and * PTPN11. References Further reading

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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 Src homology (SH)2-containing molecules. Src homology 2 domains are globular protein modules present in a large variety of functionally distinct proteins. They mediate binding events that control the activity and localization of many proteins involved in the transmission of signals from the cell surface to the nucleus. The mRNAs of these proteins are expressed ubiquitously in human adult and fetal tissues. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some variants has not been determined. Interactions RAPGEF1 has been shown to interact with: * BCAR1, * CRK, * CRKL * Grb2, and * HCK Tyrosine-protein kinase HCK is an enzyme that in humans is encoded by the ''HCK ...
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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. Mutations in ''PXN'' as well as abnormal expression of paxillin protein has been implicated in the progression of various cancers. Structure Human paxillin is 64.5 kDa in molecular weight and 591 amino acids in length. The C-terminal region of paxillin is composed of four tandem double zinc finger LIM domains that are cysteine/histidine-rich with conserved repeats; these serve as binding sites for the protein tyrosine phosphatase-PEST, tubulin and serves as the targeting motif for focal adhesions. The N-terminal region of paxillin has five highly conserved leucine-rich sequences termed LD motifs, which mediate several interactions, including that with pp125FAK and vinculin. The LD motifs are predicted to form amphipathic alpha helices, with ...
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BCR Gene
The breakpoint cluster region protein (BCR) also known as renal carcinoma antigen NY-REN-26 is a protein that in humans is encoded by the ''BCR'' gene. ''BCR'' is one of the two genes in the ''BCR-ABL'' fusion protein, which is associated with the Philadelphia chromosome. Two transcript variants encoding different isoforms have been found for this gene. Function Although the BCR- ABL fusion protein has been much studied, the function of the normal BCR gene product is still not clear. The protein has serine/threonine kinase activity and is a guanine nucleotide exchange factor for the Rho family of GTPases including RhoA. Clinical significance A reciprocal translocation between chromosomes 22 and 9 produces the Philadelphia chromosome, which is often found in patients with chronic myelogenous leukemia. The chromosome 22 breakpoint for this translocation is located within the ''BCR'' gene. The translocation produces a fusion protein that is encoded by sequence from both ''BCR'' ...
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Abl Gene
Tyrosine-protein kinase ABL1 also known as ABL1 is a protein that, in humans, is encoded by the ''ABL1'' gene (previous symbol ''ABL'') located on chromosome 9. c-Abl is sometimes used to refer to the version of the gene found within the mammalian genome, while v-Abl refers to the viral gene, which was initially isolated from the Abelson murine leukemia virus. Function The ''ABL1'' proto-oncogene encodes a cytoplasmic and nuclear protein tyrosine kinase that has been implicated in processes of cell differentiation, cell division, cell adhesion, and stress response such as DNA repair. Activity of ABL1 protein is negatively regulated by its SH3 domain, and deletion of the SH3 domain turns ABL1 into an oncogene. The t(9;22) translocation results in the head-to-tail fusion of the '' BCR'' and ''ABL1'' genes, leading to a fusion gene present in many cases of chronic myelogenous leukemia. The DNA-binding activity of the ubiquitously expressed ABL1 tyrosine kinase is regulated by ...
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Dock2
Dock2 (Dedicator of cytokinesis 2), also known as DOCK2, is a large (~180 kDa) protein involved in intracellular Cell signalling, signalling networks. It is a member of the DOCK-A subfamily of the DOCK (protein), DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G proteins. Dock2 specifically activates isoforms of the small G protein Rac (GTPase), Rac. Discovery Dock2 was first characterised as one of a number of proteins which shared high sequence similarity with the previously described protein Dock180, the archetypal member of the DOCK family. Whereas Dock180 gene expression, expression is near ubiquitous in mammals, Dock2 appears to be expressed specifically in leukocytes and is considered to be the principal DOCK family member in these cells. Structure and function Dock2 is part of a large class of proteins (GEFs) which contribute to cellular signalling events by activating small G proteins. In their resting state G proteins are b ...
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CRK (gene)
Adapter molecule crk also known as proto-oncogene c-Crk is a protein that in humans is encoded by the ''CRK'' gene. The CRK protein participates in the Reelin signaling cascade downstream of DAB1. 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 through SH2-phosphotyrosine interaction. The N-terminal SH2 domain of this protein functions as a positive regulator of transformation whereas the C-terminal 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 participates in the Reelin signaling cascade downstream of DAB1. v-Crk, a transforming oncoprotein from avian sarcoma viruses ...
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GAB2
GRB2-associated-binding protein 2 also known as GAB2 is a protein that in humans is encoded by the ''GAB2'' gene. GAB2 is a docking protein with a conserved, folded PH domain attached to the membrane and a large disordered region, which hosts interactions with signaling molecules. It is a member of the GAB/DOS family localized on the internal membrane of the cell. It mediates the interaction between receptor tyrosine kinases (RTKs) and non-RTK receptors serving as the gateway into the cell for activation of PTPN11, SHP2, Phosphatidylinositol 3-kinase (PI3K), Grb2, extracellular-signal-regulated kinase, ERK, and AKT and acting as one of the first steps in these signaling pathways. GAB2 has been shown to be important in physiological functions such as growth in bone marrow and cardiac function. GAB2 has also been associated with many diseases including leukemia and Alzheimer's disease. Discovery GAB proteins were one of the first docking proteins identified in the mammalian signal ...
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