Plateletderived Growth Factor Pdgf

with mannose phosphate. Dimerization follows to a 110-kDa inactive precursor. The precursor has to be activated in a process that is not well understood, but one that may involve proteases. TGF-/3 in serum is bound to a2-macroglobulin, which is cleared by the liver; however, the latent complex of TGF-/3 has an extended half-life and is probably activated by proteases and binding to the IGF-II receptor through substituent mannose 6-phosphate residues. This complex between latent TGF-/3 and IGF-II receptor may be the best conformational form to allow the activating proteases to attack the latent TGF-/3. Latency is apparently a function of the content of sialyl substituents. Binding of latent TGF-/3 to IGF-II receptor could also facilitate endocytosis of the complex to avail the latent TGF-/3 to the lysosomes and an activating environment. The active TGF-/3 is a 12.5-kDa peptide in the form of a 25-kDa homodimer linked by disulfide bonds.

There is a membrane-binding protein that forms a 300-kDa complex with TGF-/3. The function of the binding protein is unknown except that it contains large amounts of heparin sulfate and chondroitin sulfate. This complex may represent a storage form of TGF-/3. The signal-transducing form of TGF-/3 appears

PDGF consists of two chains, A and B, which are separate gene products joined by a disulfide bond. Consequently, three forms of PDGF exist: PDGF-AA, PDGF-AB, and PDGF-BB. The molecular weight of the dimer is about 30 kDa, the A chain being 12 kDa and the B chain 18 kDa. Human platelets contain all three isoforms. PDGF-AA has been found in the context of the osteosarcoma cell-derived growth factor (ODGF), and PDGF-BB has been found in the context of p28sis secreted by simian sarcoma virus-infected cells. PDGF-AA is a secreted form of the growth factor, whereas PDGF-BB is associated with intracellular compartments.

There are two PDGF receptors, a and f3. Both receptors have five extracellular Ig-like domains and intracellular tyrosine kinase domains (Figure 19-10). When the dimeric ligand binds to a receptor, a receptor dimer is formed that is capable of activating the signal transduction process, including autophosphorylation of intracellular tyrosine residues as an initial step. It is of interest that both receptors a and (i induce signal transduction, but only the /3-receptor is involved in chemo-taxis. The a-receptor binds both the A and B chains of PDGF, but the /3-receptor binds only the B chain of the growth factor. Thus, receptor dimer aa binds PDGF-

Cure Tennis Elbow Without Surgery

Cure Tennis Elbow Without Surgery

Everything you wanted to know about. How To Cure Tennis Elbow. Are you an athlete who suffers from tennis elbow? Contrary to popular opinion, most people who suffer from tennis elbow do not even play tennis. They get this condition, which is a torn tendon in the elbow, from the strain of using the same motions with the arm, repeatedly. If you have tennis elbow, you understand how the pain can disrupt your day.

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