Expression of transforming growth factor b1, b2, b3 in neuroendocrine tumors of the digestive system

Ligand induced activation of the beta-receptor for platelet-derived growth factor (PDGF) leads to activation of Src family tyrosine kinases. We have explored the possibility that the receptor itself is a substrate for Src. We show that Tyr934 in the kinase domain of the PDGF receptor is phosphorylated by Src. Cell lines expressing a beta-receptor mutant, in which Tyr934 was replaced with a phenyalanine residue, showed reduced mitogenic signaling in response to PDGF-BB. In contrast, the mutant receptor mediated increased signals for chemotaxis and actin reorganization. Whereas the motility responses of cells expressing wild-type beta-receptors were attenuated by inhibition of phosphatidylinositol 3'-kinase, those of cells expressing the mutant receptor were only slightly influenced. In contrast, PDGF-BB-induced chemotaxis of the cells with the mutant receptor was attenuated by inhibition of protein kinase C, whereas the chemotaxis of cells expressing the wild-type beta-receptor was less affected. Moreover, the PDGF-BB-stimulated tyrosine phosphorylation of phospholipase C-gamma was increased in the mutant receptor cells compared with wild-type receptor cells. In conclusion, the characteristics of the Y934F mutant suggest that the phosphorylation of Tyr934 by Src negatively modulates a signal transduction pathway leading to motility responses which involves phospholipase C-gamma, and shifts the response to increased mitogenicity.

Öberg, KjellUppsala universitet,Institutionen för medicinska vetenskaper,Onkologisk endokrinologi, K Öberg(Swepub:uu)kjellob (författare)
Gobl, AndersUppsala universitet,Institutionen för medicinska vetenskaper,Onkologisk endokrinologi, K Öberg (författare)
Heldin, Carl-HenrikLudwiginstitutet för Cancerforskning(Swepub:uu)carlheld (författare)
Funa, KeikoLudwiginstitutet för Cancerforskning (författare)
Uppsala universitetInstitutionen för medicinska vetenskaper (creator_code:org_t)

Av författaren/redakt...: Chaudhry, A; Öberg, Kjell; Gobl, Anders; Heldin, Carl-Hen ...; Funa, Keiko

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.