The mitogenic response to EGF of rat hepatocytes cultured on laminin-rich gels (EHS) is blocked downstream of receptor tyrosine-phosphorylation.
Hepatocytes cultured on type I collagen proliferate in response to mitogenic growth factors yet de-differentiate. By contrast, hepatocytes on laminin-rich gels (EHS) demonstrate stable differentiated functions, while DNA synthesis is negligible. Here we have confirmed that this lack of proliferation was not due to deterioration of the cells because albumin release was maintained for several weeks. Additionally it does not appear to be due to the presence of the growth inhibitor TGF beta within the gel since and anti-TGF beta antibodies did not reverse the growth blockade. The addition of EGF to cells cultured on either type I collagen or EHS gel induced increased tyrosine phosphorylation of a 180kDa protein which ran in a position identical to that of the EGF receptor detected by a specific EGF receptor antibody. We conclude that since functional EGF receptors were present, the mitogenic response of hepatocytes on EHS gels is blocked at some downstream signaling event beyond that of receptor tyrosine autophosphorylation.
Gardner
M J
MJ
School of Biochemistry, University of Birmingham, United Kingdom.
Fletcher
K
K
Pogson
C I
CI
Strain
A J
AJ
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D046508:Culture Techniques / Q000379:methods; D004247:DNA / Q000096:biosynthesis; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism*; D005782:Gels; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D007797:Laminin; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000032:analysis; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D012709:Serum Albumin / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D005782:Gels; D007797:Laminin; D011994:Recombinant Proteins; D012709:Serum Albumin; D016212:Transforming Growth Factor beta; D019000:Phosphotyrosine; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; D004247:DNA; D066246:ErbB Receptors