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Mismatch Repair Protein (MSH6)<br />

Clone PU29<br />

1 mL, 0.1 mL liquid NCL-L-MSH6 P (HIER)<br />

7 mL Bond ready-to-use PA0597 P (HIER)<br />

MSH6 is a 160 kD protein which is involved in DNA mismatch repair (MMR)<br />

and recombination pathways, when heterodimerized with MSH2. Defects in<br />

mismatch repair systems can cause mutations and can cause DNA<br />

microsatellite sequences to become unstable. Microsatellite instability has<br />

been described in colorectal cancer, particularly in Hereditary Nonpolyposis<br />

Colorectal Cancer (HNPCC) where MSH6 expression, along with other MSH<br />

proteins, is disrupted. Immunohistochemical studies have reported that<br />

MSH6 is strongly expressed in the nucleus of cells in normal colonic<br />

epithelium, especially in crypts. Expression is also found in lymphocytes.<br />

Studies have also shown that MSH6 is expressed in gastric carcinomas and<br />

endometrial carcinomas. However, sometimes expression can be lost in<br />

some endometrial carcinomas and colonic carcinomas with microsatellite<br />

instability. MSH6 has been reported to be a useful marker to use in<br />

conjunction with microsatellite instability screening to identify colon tumors<br />

that may contain MMR gene mutations, such as HNPCC.<br />

Product Specific Information<br />

The use of PBS-based diluents may result in increased background staining.<br />

Refer to page 34 for the Bond ready-to-use format.<br />

Human colonic carcinoma: immunohistochemical staining for Mismatch Repair Protein 6<br />

(MSH6) using NCL-L-MSH6. Note intense nuclear staining of a proportion of tumor cells.<br />

Paraffin section.<br />

Mismatch Repair Protein (PMS2)<br />

Clone M0R4G New!<br />

1 mL, 0.1 mL liquid NCL-L-PMS2 P (Enzyme) W<br />

Reference Range<br />

New!<br />

Postmeiotic segregation increased 2 (PMS2), also known as PMS1 protein<br />

homologue 2, is a DNA mismatch repair (MMR) protein. The PMS2 gene<br />

family members are found in clusters on chromosome 7. PMS2 is a 96 kDa<br />

mismatch repair protein closely related to MLH1, MLH3 and PMS1, which<br />

are homologs of the bacterial mutL gene. The PMS2 protein forms a<br />

heterodimer with the MLH1 protein which is then activated in the presence<br />

of ATP; this complex coordinates the binding of other proteins that repair<br />

DNA errors arising during cell preparation for cell division.<br />

The loss of PMS2 expression in tumors can be helpful in identifying hMLH1<br />

mutation carriers and identify their suitability for mutation analysis.<br />

PMS2 gene defects account for a small but significant proportion of<br />

colorectal cancers and for a substantial proportion of tumors with<br />

microsatellite instability. PMS2 is associated with cases of the dominantly<br />

inherited disorder Hereditary Non-Polyposis Colon Cancer (HNPCC) but<br />

more clearly associated with a variation of HNPCC known as Turcot<br />

syndrome.<br />

Human Colonic Carcinoma: immunohistochemical staining for PMS2 using NCL-L-PMS2.<br />

Paraffin section.<br />

Mitogen-Activated Protein Kinase<br />

Kinase 4<br />

Clone 7A6<br />

1 mL lyophilized NCL-MKK4 P (HIER)<br />

Mitogen-activated protein kinase kinase 4 (MKK4) is a member of the MAP<br />

kinase kinase family which directly phosphorylates and activates the c-Jun<br />

N-terminal kinases (JNK) in response to cellular stresses and proinflammatory<br />

cytokines. MKK4, like MKK3, also phosphorylates and activates<br />

the p38/HOG kinase. MKK4 activates mitogen-activated protein kinases<br />

(MAPKs) which are involved in the transduction of extracellular signals for<br />

g<strong>row</strong>th factors or environmental stresses which usually result in cell g<strong>row</strong>th<br />

and differentiation. MKK4 mRNA has been reported to be expressed in many<br />

human tissues including skeletal muscle and brain with lower expression in<br />

heart, placenta, kidney, liver, pancreas, and in the cytoplasm and nucleus of<br />

normal gastric epithelia. The deletion and mutation of the MKK4 gene,<br />

reported in human pancreatic lung, breast, testicle and colorectal cancer<br />

cell lines and in a proportion of gastric, prostatic, pancreatic, biliary and<br />

breast carcinomas, suggests that it might have a role as a suppressor of<br />

tumorigenesis or metastasis.<br />

Human testis: immunohistochemical staining for mitogen-activated protein kinase kinase 4<br />

using NCL-MKK4. Note cytoplasmic and nuclear staining of spermatogonia in the seminiferous<br />

tubules. Paraffin section.<br />

F Frozen I Immunofluorescence E Electron microscopy<br />

P Paraffin C Flow cytometry O Other applications<br />

W Western blotting<br />

/ 135<br />

Primary Antibodies

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