CD332 FGFR2 (fibroblast growth factor receptor 2) KGFR (keratinocyte growth factor receptor) TK14, TK25, BEK (bacteria expressed kinase), JWS, CEK3, CFD1, ECT1, BFR-1, KSAM
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Epithelial Cell
Fibroblast
Kidney
Lung
Prostate
Spinal cord
Liver
Mesenchymal Cell
Brain
115 / 115
135 / 135

Expression
CD332 is expressed on fibroblasts, mesenchymal cells and epithelial cells.  Expression is in the brain, liver, prostate, kidney, lung and spinal cord.

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

CD332 is a single-pass type-1 800 aa glycoprotein.  It contains a 356 aa extracellular domain which contains 3 Ig-like C2-type domains and 8 N-linked glycosylation sites a 21 aa transmembrane domain and a 423 aa intracellular cytoplasmic domain composed of 2 ATP binding sites and a 290 aa tyrosine kinase domain that is split by a short insert.  The 3 Ig-like C2-type domains (D1-D3), a stretch of residues in the linker connecting D1 and D2 known as the "acid box", a heparin binding site in D2.  D2 and D3 form the primary binding pocket for fibroblast growth factor (FGF), whereas D1 and the acid box have an autoinhibitory role.  Binding FGF induces dimerization of CD332 and results in a tetrameric complex.  Essential cofactors associated with this complex are cell-surface heparin sulphate proteoglycans.  CD332 interacting with FGF sets in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation.  It is a transmembrane tyrosine kinase that serves as a high affinity receptor for FGFs.  FGFs are mitogens that can activate a number of intracellular signalling pathways and exert numerous effects depending on the target cell.  The protein encoded by this gene, CD332, is a member of the FGFR family, where the amino acid sequence is highly conserved between members and throughout evolution.   CD332 family members differ from one another in their ligand affinities and tissue distribution.  The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. 

MOLECULAR MASS

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 19 different isoforms by RNA splicing.  However, not all isoforms have been fully characterized but the most significance is the cell-type specific obligatory splicing that generates two forms of D3 with different FGF binding characteristics.

POST-TRANSLATIONAL MODIFICATION

CD332 has 8 potential N-linked glycosylation sites.  Dimerization promotes autophosphorylation in trans of critical tyrosines in the activation loop that stablizes the receptor in an active conformation and leads to in cis phosphorylation of tyrosine residues within the TK domain.  Intracellular phosphotyrosines serve as binding sites for signal transduction molecules such as SHC, FRS2 and phospholipase Cγ (PLCγ). 

Ligands
LIGANDS AND MOLECULE ASSOCIATED WITH CD332

CD332 binds acidic and basic fibroblast growth factors with high affinity.

Function
CD332 serves as a high affinity receptor for fibroblast growth factors (FGFs).  They are mitogens that can activate a number of intracellular signalling pathways and exert numerous effects depending on the target cell.  The receptor proteins play a role in important processes such as cell division, regulation of cell growth and maturation, and formation of blood vessels. 

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD331 IN INTACT ANIMAL

This particular family member binds both acidic and basic fibroblast growth factors.  The interaction between FGFs and FGFRs is very important in the development of the embryo and in wound healing.  During development of the embryo, FGF-induced CD332-mediated signaling plays a critical role in morphogenesis by regulating cell proliferation, differentiation and migration.  In adults, CD332 mediated signaling is involved in tissue repair and wound healing, tumor angiogenesis and tumor growth.  Null mutations of CD332 in mice are embryonic lethal due to defective cell migration through the primitive streak and a posterior axis defect.  Selective disruption results in death of the mice immediately after birth and is characterized by defective development of lungs, limbs, anterior pituitary, thyroid and teeth.  Targeted disruption of CD332 leads to viable mice with impaired skull and bone development.  In humans, mutations are associated with a variety of human skeletal disorders including Crouzon syndrome, Jackson-Weiss syndrome, Apert syndrome, Beare-Stevenson cutis gyrata, Pfeiffer syndrome and Saethre-Chotzen-like syndrome.  Many of these syndromes are specific nucleotide substitutions and have been found to be germline mutations of paternal origin.  A downregulation of CD332 expression is observed in malignant astrocytomas. Mutations are associated with prostate cancer and gastric cancer.




 

Comments
MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD332: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD332: No information.

ADDITIONAL INSIGHTS

For further information see Wlash, S. et al (2000) Bone 27: 185-195.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 2263P21802
Antibodies

Revised June 25, 2008


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