Tyrosine kinase growth factor receptors but not seven-membrane–spanning receptors or phorbol esters activate mitogen-activated protein kinase in rat hepatocytes
✍ Scribed by Dr Pere Ginès; Xiaomei Li; Jeffrey L. Zamarripa; Susan E. S. Brown; Eric D. Wieder; Toshikazu Nakamura; Phillip S. Guzelian; Robert W. Schrier; Lynn E. Heasley; Raphael A. Nemenoff
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- English
- Weight
- 1012 KB
- Volume
- 22
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
The response of rat hepatocytes to hormones and growth factors has been extensively studied with respect to phospholipase regulation and calcium mobilization. However, the mitogen-activated protein (MAP) kinase cascade which integrates signals from a wide variety of extracellular stimuli has not been examined in these cells. Thus, in the present study the pathways leading to activation of MAP kinase in primary cultures of adult rat hepatocytes were investigated. Growth factors acting through tyrosine kinase receptors (epidermal growth factor and hepatocyte growth factor) increased Raf and MAP kinase activity through a protein kinase C and calcium-independent pathway. Agonists acting through seven-membrane-spanning receptors (arginine vasopressin and angiotensin 11) increased intracellular calcium concentration but did not stimulate Raf or MAP kinase activity. Arginine vasopressin, however, stimulated MAP kinase activity in rat l a fibroblasts transfected with the hepatic V1, receptor and in rat aortic vascular smooth muscle cells. Phorbol 12-myristate 13-acetate (PMA) was also unable Abbreviations: EGF, epidermal growth factor; HGF, hepatocyte growth factor; PLC, phospholipase Cy; AVP, arginine vasopressin; MI, angiotensin 11; MAP, mitogen-activated protein; MEK, MAP kinase kinase; PKC, protein kinase C; MEKK, distinct family of MEK kinases; PMA, phorbol 12-myristate 13-acetate; MBP, myelin basic protein; PKI, protein kinase inhibitor peptide; BAPTA, 1,Z-bis (2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid; VSMC, vascular smooth muscle cells.