Ligand-induced interaction between. alpha. - and. beta. -type platelet-derived growth factor (PDGF) receptors: Role of receptor heterodimers in kinase activation

Journal Article · Tue Feb 19 00:00:00 EST 1991 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00221a005· OSTI ID:5397884

Kanakaraj, P; Raj, S; Bishayee, S ^[1]; Khan, S A ^[2]

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1. Coriell Institute for Medical Research, Camden, NJ (USA)
2. Wistar Institute, Philadelphia, PA (USA)

Two types of PDGF receptors have been cloned and sequenced. Both receptors are transmembrane glycoproteins with a ligand-stimulatable tyrosine kinase site. The authors have shown earlier that ligand-induced activation of the {beta}-type PDGF receptor is due to the conversion of the monomeric form of the receptor to the dimeric form. In the present studies, they have established the ligand-binding specificity of two receptor types and extended it further to investigate the ligand-induced association state of the {alpha}-receptor and the role of {alpha}-receptor in the activation of {beta}-receptor. These studies were conducted with cells that express one or the other type of PDGF receptor as well as with cells that express both types of receptors. Moreover, ligand-binding characteristics of the receptor were confirmed by immunoprecipitation of the receptor-{sup 125}I-PDGF covalent complex with type-specific anti-PDGF receptor antibodies. These studies revealed that all three isoforms of PDGF bind to {alpha}-receptor, and such binding leads to dimerization as well as activation of the receptor. In contrast, {beta}-receptor can be activated only by PDGF BB and not by PDGF AB or PDGF AA. However, by using antipeptide antibodies that are specific for {alpha}- or {beta}-type PDGF receptor, they demonstrated that in the presence of {alpha}-receptor, {beta}-receptor kinase can be activated by PDGF AB. They present here direct evidence that strongly suggests that such PDGF AB induced activation of {beta}-receptor is due to the formation of a noncovalently linked {alpha}-{beta} receptor heterodimer.

• OSTI ID: 5397884
• Journal Information: Biochemistry; (United States), Vol. 30:7; ISSN 0006-2960
• Country of Publication: United States
• Language: English

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