CD136 MST1R (macrophage stimulating 1 receptor (c-met-related kinase)), RON, MSP-R, CDw136
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Epithelial Cell
Hematopoietic Cell
Neuroendocrine Cell
Macrophage
Skin
Kidney
Lung
Liver
Colon
Small intestine
Keratinocyte
Monocyte
Granulocyte
150 / 150
185 / 185

Expression
CD136 (was CDw136) is expressed mainly on epithelial tissues including skin, kidney, lung, liver, intestine and colon and is expressed on certain established hematopoietic cells, neuroendrocine cells and keratinocytes.  Expression is on monocytes, granulocytes and resident macrophages.



Structure
MOLECULAR FAMILY NAME: Belongs to the tyrosine kinase receptor family.

CD136 is a single-chain type-1 1400 aa heterodimeric glycoprotein.  It contains 3 IPT/TIG domains that have Ig-like folds and a Sema domain.  There is an a chain and β chain are cleaved from a single gene product and are linked by a disulfide bond.  The α chain is located extracellularly and the b chain consists of an extracellular domain, a transmembrane segment and an intracellular tyrosine kinase domain.  CD136 is a member of the hepatocyte growth factor receptor subgroup of the receptor kinase family. 

MOLECULAR MASS
Cell Type Unreduced Reduced Comment
Epithelial cells 185 kDa (α chain)  150 kDa (a chain), 40 kDa (b chain)
Resident macrophages 185 kDa (α chain)  150 kDa (a chain), 40 kDa (b chain)

CD136 has 2 "chains" or "fragments" which result from the cleavage of a single gene product.

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 2 different isoforms.  Splicing of the transcript results in a truncated protein with an in-frame deletion of 49 aa in the extracellular domain of the b chain.

POST-TRANSLATIONAL MODIFICATION

CD136 contains a 185 kDa single chain precursor with glycosylation at the N-terminus.  Proteolytic cleavage into the 2 chain form is linked by a disulfide bond.  Ligand-dependent tyrosine phosphorylation of the kinase domain is in the b chain.

Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD136
Molecule Comment
MSP (macrophage stimulating protein) Purified serum protein which induces migration and shape change of mouse peritoneal resident macrophages
HGF1 (hepatocyte growth factor-like) A cloned gene encoding an unknown protein with similar structure to HGF
PLC-g Association, possible substrate
Shc Association, possible substrate



Function
CD136 is the receptor for macrophage stimulating protein (MSP).  Ligation-induced receptor dimerization induces cell migration, morphological change, cell growth, cytokine induction, and proliferation. The tyrosine kinase transmits apoptosis in different target cells as well as growth signals.  CD136 is involved in the regulation of production of blood cells and in the development of epithelial tissue.  It  may also regulate ciliary beat frequency in epithelial cells.

BIOCHEMICAL ACTIVITY

There is an increased kinase activity upon ligand-induced receptor dimerization.

DISEASE RELEVANCE AND FUNCTION OF CD136 IN INTACT ANIMAL

CD136 null mice fail to survive the peri-implantation period.  CD136 +/- mice are highly susceptible to endotoxic shock.

Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD136: No information.

SUBSTRATES
Molecule Comment
Grb2/Sos Translocation from cytosol to membrane and activation of Ras
PI-3 kinase Interaction with activated receptors and involvement in cell migration

ENZYMES WHICH MODIFY CD136: No information.

ADDITIONAL INSIGHTS

Important areas of investigation are the physiological function of CD136 RON in vivo, the role in inflammation and wound healing and the mechanisms of activation in invasive growth and movement of epithelial tumors.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 4486Q04912
Antibodies

Revised June 25, 2008


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